POTASSIUM A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Potassium: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84174-8 1. Potassium-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on potassium. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON POTASSIUM ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Potassium...................................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 62 The National Library of Medicine: PubMed ................................................................................ 72 CHAPTER 2. NUTRITION AND POTASSIUM ................................................................................... 107 Overview.................................................................................................................................... 107 Finding Nutrition Studies on Potassium .................................................................................. 107 Federal Resources on Nutrition ................................................................................................. 111 Additional Web Resources ......................................................................................................... 111 CHAPTER 3. ALTERNATIVE MEDICINE AND POTASSIUM ............................................................. 123 Overview.................................................................................................................................... 123 National Center for Complementary and Alternative Medicine................................................ 123 Additional Web Resources ......................................................................................................... 131 General References ..................................................................................................................... 144 CHAPTER 4. DISSERTATIONS ON POTASSIUM ............................................................................... 145 Overview.................................................................................................................................... 145 Dissertations on Potassium ....................................................................................................... 145 Keeping Current ........................................................................................................................ 155 CHAPTER 5. PATENTS ON POTASSIUM .......................................................................................... 157 Overview.................................................................................................................................... 157 Patents on Potassium................................................................................................................. 157 Patent Applications on Potassium............................................................................................. 190 Keeping Current ........................................................................................................................ 230 CHAPTER 6. BOOKS ON POTASSIUM.............................................................................................. 231 Overview.................................................................................................................................... 231 Book Summaries: Federal Agencies............................................................................................ 231 Book Summaries: Online Booksellers......................................................................................... 247 The National Library of Medicine Book Index ........................................................................... 253 Chapters on Potassium .............................................................................................................. 254 CHAPTER 7. MULTIMEDIA ON POTASSIUM ................................................................................... 257 Overview.................................................................................................................................... 257 Video Recordings ....................................................................................................................... 257 Audio Recordings....................................................................................................................... 260 Bibliography: Multimedia on Potassium ................................................................................... 260 CHAPTER 8. PERIODICALS AND NEWS ON POTASSIUM ................................................................ 261 Overview.................................................................................................................................... 261 News Services and Press Releases.............................................................................................. 261 Newsletters on Potassium.......................................................................................................... 264 Newsletter Articles .................................................................................................................... 265 Academic Periodicals covering Potassium ................................................................................. 266 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 267 Overview.................................................................................................................................... 267 U.S. Pharmacopeia..................................................................................................................... 267 Commercial Databases ............................................................................................................... 269 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 273 Overview.................................................................................................................................... 273 NIH Guidelines.......................................................................................................................... 273 NIH Databases........................................................................................................................... 275
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Other Commercial Databases..................................................................................................... 278 The Genome Project and Potassium........................................................................................... 278 APPENDIX B. PATIENT RESOURCES ............................................................................................... 289 Overview.................................................................................................................................... 289 Patient Guideline Sources.......................................................................................................... 289 Finding Associations.................................................................................................................. 296 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 299 Overview.................................................................................................................................... 299 Preparation................................................................................................................................. 299 Finding a Local Medical Library................................................................................................ 299 Medical Libraries in the U.S. and Canada ................................................................................. 299 ONLINE GLOSSARIES................................................................................................................ 305 Online Dictionary Directories ................................................................................................... 309 POTASSIUM DICTIONARY ...................................................................................................... 311 INDEX .............................................................................................................................................. 415
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with potassium is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about potassium, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to potassium, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on potassium. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to potassium, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on potassium. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON POTASSIUM Overview In this chapter, we will show you how to locate peer-reviewed references and studies on potassium.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and potassium, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “potassium” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Dialysate Potassium Source: Seminars in Dialysis. 4(1): 46-51. January-March 1991. Summary: Dialysis assumes a major role in potassium homeostasis in patients with endstage renal disease (ESRD). This review examines the role of dialysate potassium in maintaining potassium balance in hemodialysis patients. Topics include potassium balance in ESRD, hyperkalemia in ESRD, blood transfusion and potassium, potassium removal during hemodialysis, potassium and base interaction during hemodialysis, arrhythmias and dialysate potassium, and hypokalemia and hemodialysis. 36 references.
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ACE Inhibition or Angiotensin Receptor Blockade: Impact on Potassium in Renal Failure Source: Kidney International. 58(5): 2084-2092. November 2000. Contact: Available from Blackwell Science, Inc. Journals Fulfillment Department, 350 Main Street, Malden, MA 02148. (781) 388-8250. Summary: Inhibition of the renin angiotensin system is known to raise serum potassium (K+) levels in patients with renal insufficiency or diabetes. This study evaluates the comparative effects of an angiotensin converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum K+ in people with renal (kidney) insufficiency. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasians, mean age 56 years plus or minus 2 years) participated in the double crossover study. For the total group serum potassium level changes were not significantly different between the lisinopril (an ACE inhibitor) and valsartan (an ARB) treatments. The subgroup with glomerular filtration rate (a measure of kidney function) values of less than 60 milliliters per minute per 1.73 m-squared who received lisinopril demonstrated significant increases in serum potassium above the mean baseline. This increase in serum potassium was also accompanied by a decrease in plasma aldosterone. The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum potassium; this represents a 43 percent lower value when compared with the change in those who received lisinopril. The authors conclude that, in the presence of renal insufficiency, the ARB valsartan did not raise serum potassium to the same degree as the ACE inhibitor lisinopril. 4 figures. 3 tables. 29 references.
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Truth About Potassium Source: TransDial. 4(4): 6. Winter-Spring 1990. Summary: Potassium is a mineral that is found in almost all foods. Although healthy kidneys maintain a normal balance of potassium in the body, diseased kidneys are unable to get rid of potassium adequately. Elevated blood potassium levels can cause an irregular heartbeat and can even cause heart failure. This brief article contains a list of foods that are very high in potassium and should be avoided by the person on hemodialysis. A second list of alternative foods that are more limited in potassium content is included. For each food on the list, the portion size and amount of potassium is noted.
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Physiological Effects of Slow Release Potassium Phosphate for Absorptive Hypercalciuria: A Randomized Double-Blind Trial Source: Journal of Urology. 160(3, Part 1): 664-668. September 1998. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article describes a prospective, double blind, placebo controlled study that examined the physiological effects and tolerance of a slow release neutral form of potassium phosphate, UroPhos-K, in 31 patients with absorptive hypercalciuria (abnormally large amounts of calcium in the urine). All patients were first admitted to a research center for a control phase and placed on a constant metabolic diet with a daily composition of 400 milligrams (mg) calcium, 800 mg phosphate, and 100 mEq. sodium. After the control phase, patients were randomized into a group comprising 18 patients who took four tablets of UroPhos-K twice daily with breakfast and bedtime snack for 3 months (Group 1) and a group comprising 13 patients who took four placebo tablets
Studies
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twice daily for 3 months (Group 2). The study found that treatment with UroPhos-K did not cause significant gastrointestinal side effects, increase fasting serum potassium or phosphorus, or reduce hemoglobin or creatinine clearance. However, UroPhos-K reduced urinary calcium excretion by 111 mg per day and reduced serum 1,25dihydroxyvitamin D concentration by 16 percent. Indexes of intestinal calcium absorption and markers of bone turnover also decreased modestly. None of these changes were seen in the placebo group. The article concludes that, in patients with absorptive hypercalciuria, UroPhos-K seems to correct hypercalciuria by a combination of reduced intestinal absorption, bone resorption, and improved renal calcium reabsorption. The drug is well tolerated compared to placebo. 1 figure. 3 tables. 20 references. •
NuLYTELY (PEG 3350, Sodium Chloride, Sodium Bicarbonate and Potassium Chloride for Oral Solution) Source: Gastroenterology Nursing. 14(4): 200-203. February 1992. Summary: This article describes NuLYTELY, a new product that represents an effective alternative for bowel cleansing prior to colonoscopy that may be more acceptable to some patients than the standby, GoLYTELY. NuLYTELY, a product from Braintree Laboratories, is a modification of GoLYTELY that has been found to have the same therapeutic advantages in terms of safety, efficacy, speed, and patient acceptance. The author discusses the indications, pharmacokinetics and mechanism of action, clinical efficacy, adverse effects, dosage, contraindications and precautions, and nursing considerations for NuLYTELY. 8 references. (AA-M).
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Potassium Tips and Facts Source: Ostomy Quarterly. 31(1): 38-40. Winter 1993. Contact: Available from United Ostomy Association. 36 Executive Park, Suite 120, Irvine, CA 92714-6744. (800) 826-0826 or (714) 660-6744. Summary: This article provides nutrition information about potassium. Written for readers with ileostomies, the article describes how the body uses potassium and why people with ileostomies should increase their intake of potassium-rich foods and fluids during times of fluid loss. The author then details ten steps to prevent diarrhea and avoid dehydration. Other topics addressed include early and late signs of dehydration; food choices for increasing potassium intake; and knowing when to consult a health care provider about problems with dehydration. The article also includes three recipes: Frozen Bananas; Half-Time Snack; and Uncle Sam Muffins.
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Does the Potassium Stimulation Test Predict Cystometric, Cystoscopic Outcome in Interstitial Cystitis? Source: Journal of Urology. 168(8): 556-557. August 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study that establishes the relationship among symptom duration, cystometric and cystoscopic findings, and the potassium stimulation test in patients with interstitial cystitis (IC). The authors performed a retrospective chart review of 189 patients who were treated at an ambulatory clinic between 1992 and 1998. Of the 189 patients diagnosed with IC, 173 (92 percent) were female and 16 (8 percent) were male. The potassium stimulation test was positive in 105 patients (83 percent),
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negative in 16 patients (13 percent) and equivocal in 6 patients (4 percent). A cystometrogram and potassium stimulation test were done in 118 patients. Bladder capacity averaged 259 milliliters in patients with tests potassium positive and negative, while average bladder volume at first sensation to void was 85 milliliters and 148 milliliters in those with negative and positive tests, respectively. Among the 102 patients with a positive potassium stimulation test, 52 had normal cystoscopic findings. The authors conclude that the potassium stimulation test is not correlated with either bladder capacity or cystoscopic findings. Nevertheless, considering that no specific diagnostic test exists for IC, the authors have found the potassium stimulation test to be helpful in cases when clinical presentation is challenging. 2 tables. 8 references. •
Prevention of Spinal Bone Loss by Potassium Citrate in Cases of Calcium Urolithiasis Source: Journal of Urology. 168(7): 31-34. July 2002. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: This article reports on a study undertaken to determine if potassium citrate treatment stabilizes spinal bone density among patients with recurrent calcium oxalate nephrolithiasis (kidney stones consisting of calcium oxalate). The authors studied a group of 16 men and 5 women with stones taking potassium citrate from 11 to 120 months. This group represented all patients from the authors' Stone Clinic who took potassium citrate alone for at least 11 months. L2-L4 bone mineral density data before and after potassium citrate treatment were retrieved retrospectively and analyzed. In the combined group L2-L4 bone mineral density increased significantly by 3.1 percent over a mean duration of 44 months. Urinary pH, citrate and potassium increased significantly during treatment, but urinary calcium did not change. The authors conclude that potassium citrate, a commonly used drug for the prevention of recurrent nephrolithiasis, may avert age dependent bone loss. Spinal bone density increased in most patients when it normally decreases. 1 figure. 3 tables. 22 references.
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Too Much Potassium Can Kill You! Source: Renalife. 8(2): 16-18. 1993. Summary: This patient education article explores the problems of potassium levels in people on dialysis. After a review of the physiological role of potassium, the authors discuss why monitoring potassium is so important for dialysis patients. Topics include dietary restrictions, normal blood levels of potassium, the psychosocial factors associated with limited diets, and the importance of working closely with a dietitian. A list of high potassium foods, separated into the categories of dairy products, fruits, vegetables, and miscellaneous, is also included.
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Potassium Source: Journal of Renal Nutrition. 1(3): 144-145. July 1991. Summary: This patient education chart, suitable for photocopying and distribution to patients, reviews the role of potassium in the diets of people with kidney disease. The chart lists high-potassium foods and low-potassium foods in three categories: fruits, vegetables, and other foods. The authors caution that nearly all foods contain some potassium, so that a large portion of a low-potassium food may function as a highpotassium food.
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Federally Funded Research on Potassium The U.S. Government supports a variety of research studies relating to potassium. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to potassium. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore potassium. The following is typical of the type of information found when searching the CRISP database for potassium: •
Project Title: ANESTHETICS EFFECTS ON ISCHEMIC MYOCARDIUM Principal Investigator & Institution: Warltier, David C.; Professor; Anesthesiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 31-JUL-2004 Summary: (adapted from applicant's abstract) The long-term objective of this work is a comprehensive analysis of the cardioprotective effects of volatile anesthetics. These agents are capable of reducing the contractile deficit (myocardial stunning) following a brief period of ischemia and the extent of myocardial infarction following a prolonged period of coronary artery occlusion. Recently, it was found that a prior, brief exposure to the volatile anesthetic, isoflurane, could reduce myocardial infarct size after its discontinuation. This phenomenon has a strong similarity to ischemic preconditioning, in which a brief period of coronary artery occlusion and reperfusion renders myocardium resistant to infarction after a subsequent prolonged ischemia insult. Anesthetic-induced preconditioning (APC) demonstrates a powerful cardioprotective effect with short and long-term memories. The major hypothesis to be tested in the present investigation is that volatile anesthetics directly produce early and late preconditioning against both myocardial stunning and infarction via enhanced opening of ATP-dependent potassium (KATP) channels. Signal transduction pathways including adenosine receptors and protein kinase C serving as a mechanism(s) for APC will be characterized. APC-induced alterations in the interstitial concentration of adenosine and translocation of PKC isoforms will be measured in ischemic and control myocardium. Cardioprotective effects of the anesthetics will be studied in in vivo canine models of myocardial ventricular pressure-segment length diagrams, and myocardial infarct size will be measured by triphenyl tetrazolium histochemical staining. Alterations in potassium conductance through KATP channels will be studied directly by means of modification of the patch clamp technique in normal and previously ischemic ventricular myocytes. Because of the large number of patients with coronary artery disease undergoing infarction, the proposed research represents an investigation into a clinically relevant problem. Isoflurane has recently been shown to produce APC in
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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patients undergoing coronary artery bypass graft surgery. Thus, this proposal will delineate mechanisms responsible for the novel and unique cardioprotective effects of volatile anesthetics against ischemia and reperfusion injury in vivo and provide direct evidence of the involvement of specific signal transduction pathways modulating the KATP channel in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SECRETION
ATP-SENSITIVE
POTASSIUM
CHANNELS
AND
INSULIN
Principal Investigator & Institution: Shyng, Show-Ling; Assistant Scientist; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: The pancreatic ATP-sensitive potassium channels (KATP channels) control insulin secretion in B-cells. The long-term goal is to understand how KATP channels are regulated at the molecular level to control insulin secretion. In addition to being regulated by intracellular ATP and ADP, a property, which enables the channel to couple, cell energy to cell excitability, the investigators recently showed that the channel is profoundly regulated by membrane phosphoinositides. Phosphoinositides modulate the sensitivity of KATP channels to ATP over several orders of magnitude. This modulation provides a mechanism to allow channels to be gated by physiological concentrations of ATP and ADP. Relative to regulation by intracellular nucleotides, our understanding of channel regulation by phosphoinositides is still in its infancy. The research proposed is aimed at understanding the physiological significance and the molecular basis of this novel regulatory mechanism. To assess the physiological significance, the investigators will manipulate membrane phosphoinositide levels in insulin-secreting cells and-examine the effects on channel activity and insulin secretion. The investigators will also disrupt the interaction between phosphoinositides and channels in these cells by overexpressing mutant channels lacking the ability to interact with phosphoinositides, and inhibitory peptides that compete with endogenous channels for phosphoinositide binding, and evaluate the physiological outcome. The investigators will determine the structural elements within the channel proteins involved in phosphoinositide regulation using systematic site-directed mutagenesis approach combined with electrophysiolgical measurements that monitor functional interaction between the channel and phosphoinositides, and with biochemical measurements that monitor the physical interaction between the channel and phosphoinositides. The information we propose to obtain is crucial for understanding KATP channel regulation and, hence, insulin secretion. It will provide insights to novel therapeutic approaches to diseases of insulin secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTOREGULATION AND HYPOXIC DILATION IN THE BRAIN Principal Investigator & Institution: Harder, David R.; Director; Physiology; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract) The overall goal of the application is to define the role of products of a cytochrome P450 w-hydroxylase enzyme located in cerebral arterial muscle in mediating pressure-induced activation and hypoxia-induced inhibition of the cerebral vasculature. They will test the hypothesis that autoregulation of cerebral blood flow and the cerebral vascular response to hypoxia are mediated by a
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common mechanism involving regulation of smooth muscle potassium channel activity and membrane potential. They plan to test the ability of the cerebral vasculature to form the P450 w-hydroxylase product 20-HETE upon elevation of transmural and arterial pressure, and the ability of reduced PO2 to inhibit such production. They also plan to determine if the action of hypoxia, and the parenchymal/endothelial factors released by hypoxia involves increasing potassium channel activity and hyperpolarizing the vascular muscle membrane. They will also determine if there is linkage between increased P450 w-hydroxylase activity in response to increasing transmural pressure and the cerebral vascular responses to changes in PO2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOCHEMICALLY DETERMINED TOPOLOGY OF AN RENAL K+ CHANNEL Principal Investigator & Institution: Schwalbe, Ruth A.; Biochem and Molecular Biology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-MAY-2003 Summary: The long-term goal is to determine the topology of a kidney potassium channel critical to body floud homeostasis and relate the topology to ion conduction and modulation. The specific aims are to: 1)examine the validity of an alternative topological model that I have proposed to ROMK1; 2) investigate my model's implications for ion conduction; 3) determine whether the topology of IRK1 is similar to ROMK1. The health-relatedness of the project derives from ROMK1 being critical to potassium secretion in the kidney. A hereditary hypokalemia due to a mutant renal NA/K/Cl cotransporter has already been reported. ROMK1 may likewish be implicated in hereditary renal disease. The experimental design is to map the extracellular segments by N-glycosylaton substitution mutagenesis and epitope mapping, and to verify the predicted intracellular segments by protease digestion for ROMK1, as well as IRK1. Functional studies will test whether mutations or modifications of the Asn residues with or without carbohydrate alter the biophysical properties. The research methods combine: recombinant DNA to engineer N-glycosylation substitution mutants; expression of recombinant proteins in Spodoptera frugiperda (Sf9) cells and Xenopus oocytes; biochemical methods for ascertaining glycosylation; and patch clamp measurements of the hererologously expressed currents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CA2+ SPARKS & URINARY BLADDER SMOOTH MUSCLE EXCITABILITY Principal Investigator & Institution: Nelson, Mark T.; Professor and Chair; Pharmacology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2007 Summary: (provided by applicant): Detrusor instability is a major component of urinary bladder dysfunction, including outflow obstruction associated with benign prostate hyperplasia. The goal of this project is to understand the normal physiological regulation of urinary bladder smooth muscle (UBSM) excitability and to apply an experimental model of partial urinary outflow obstruction to address pathophysiological aspects of UBSM function. This proposal focuses on the communication among four key ion channels involved in regulating the excitationcontraction (E-C) coupling process in UBSM: 1) Voltage-dependent calcium channels
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(VDCC), which mediate the upstroke of the UBSM action potential. 2) Ryanodinesensitive calcium release channels in the sarcoplasmic reticulum (RyRs), which release Ca2+ in the form of Ca2+ sparks. 3) Large-conductance, voltage/calcium-activated potassium (BK) channels, which mediate membrane repolarization of an action potential. 4) Small-conductance, calcium-activated (SK) channels, which are responsible for the after-hyperpolarization. This work builds on our discovery of Ca2+ sparks and their communication to BK channels in smooth muscle, and elucidation of key molecular components of this process. In an important advancement, we have found that the beta 1-subunit of the BK channel plays a major role by tuning the voltage/Ca2+ -sensitivity of this channel. We provide novel evidence that the BK channel beta 1-subunit and SK channels have profound effects on bladder function; data that point to potassium channel dysfunction as a significant contributor to detrusor instability following obstruction. An integrated approach, combining molecular and electrophysiological studies with functional measures of bladder contractility and cystometric parameters, will be applied using wild-type and genetically engineered mouse models. Our specific objectives are to elucidate the functional communication among VDCCs, RyRs and BK channels in normal and outflow obstructed bladders (Aim 1), to characterize the role of the beta 1-subunit in tuning the Ca2~ and voltage sensitivity of the BK channel (Aim 2), and to defme the roles of SK channels in the regulation of UBSM function (Aim 3). The long-term goal is to develop novel approaches for regulating urinary bladder function, with the main focus being on the therapy of detrusor instability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CALCIUM ACTIVATED POTASSIUM CHANNELS Principal Investigator & Institution: Lingle, Christopher J.; Professor; Anesthesiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 21-MAY-1993; Project End 31-DEC-2001 Summary: The aim of this work is to understand the functional and structural properties of an inactivation form of a large-conductance calcium (Ca2+)- and voltage-activated potassium (K+) channel (termed BK channel). BK channels play a critical role in coupling changes in submembrane Ca2+ concentrations to changes in membrane potential and excitability. BK currents among different cells exhibit markedly different apparent Ca2+ sensitivities and much of the functional diversity remains to be explained. In contrast to most previously described BK channels, most BK channels in rat chromaffin cells exhibit rapid inactivation (BKi). BKi channels are also found in the pancreas and hippocampus. The mechanism of inactivation appears to differ from mechanisms proposed for other voltage-gated channels. Using methods of electrophysiology combined with molecular biology and biochemistry, this project will define a likely inactivation mechanism and attempt to define the composition of BKi channels. First, the possible locations of barriers to ion permeation that occur during inactivation will be determined. Second, the extent to which inactivation is coupled to conformational changes associated with channel opening will be determined. Third, possible key structural components of BKi channels will be examined. Finally, the distribution and function of BKi channels in other tissues will be determined. This project will provide new information about a mechanistically unique form of channel inactivation. Furthermore, new information will be gained about possible structural changes associated with BK gating. In different tissues, BK channels contribute to regulation of neuronal excitability, smooth muscle relaxation, and hormone secretion. The BK channel is therefore of potential medical importance, not only because it may
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serve as an important therapeutic target but also altered function of this channel may contribute to pathological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIAC SURGICAL ISCHEMIA: BIOPHYSICAL ASPECTS Principal Investigator & Institution: Krukenkamp, Irvin B.; Director, Heart Center; Surgery; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Most cardiac surgical procedures require induction and management of myocardial ischemia and reperfusion. Preconditioning by a brief period of unprotected ischemia and reperfusion confers myocardial protection subsequent to a more prolonged insult. The central hypothesis of this application is that understanding the changes in sarcolemmal membrane currents which underlie the ability of the myocyte to maintain excitability consequent to preconditioning may provide an avenue for new approaches to myocardial protection that would improve myocyte function as well as survival. Our novel models use guinea pig myocytes isolated preischemically, prior to metabolic inhibition by NaCN, and rabbit myocytes first exposed to global ischemia, and then isolated during reperfusion. Studies of intracellular calcium and pH, and sarcolemmal current-voltage relations demonstrate an increase in an outward potassium current that appears either during prolonged ischemia, or during reperfusion. This current is not blocked by glybenclamide, indicating an identity other than i(kATP) Ischemic preconditioning shortens the time to appearance of the current during ischemia, and prevents its expression during reperfusion. Using these biological markers, our specific aims are to study, 1.) whether preconditioning triggers intracellular calcium, pH, or potassium conductance changes evident during preischemia, 2.) whether depolarizing (K+ or K+/Mg ++) and/or hyperpolarizing (pinacidil or ACh) cardioplegic ischemia imparts protection by sarcolemmal conductance and intracellular ionic changes similar to preconditioning evident during reperfusion, and 3.) whether maintenance of a specific membrane potential during ischemia limits deleterious biophysical changes, and whether i(kl) or other inward rectifiers may act as mediators of the observed K+ current changes. This translational research effort supports our long-term aim to understand the biophysical mechanisms and triggers that will direct the development of specific methods to enhance the clinical conduct and outcome of cardiac ischemia for patients who must undergo surgical repair. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIAC TOXICITY OF PHOSPHOLIPID METABOLITES Principal Investigator & Institution: Stimers, Joseph R.; Associate Professor; Pharmacology and Toxicology; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract). The goal of this project is to investigate the role of the phospholipid metabolites, leukotoxin (Lx), and leukotoxindiol (Lx-diol) in the heart. Leukotoxin is an epoxide ring derivative of linoleic acid, a common component of cell membranes, formed by leukocytes in severely burned patients and during normal myocardial ischemia. Plasma levels of Lx have been correlated with late stage multiple organ failure in burn patients. One consequence is vascular collapse and cardiac arrest. Recently, Lx has been shown to cause cardiac arrest
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in dogs. Recent experiments in a cultured cell model have suggested that for Lx to be cytotoxic, it must first be metabolised to Lx-diol by a soluble epoxide hydrolase (sEH). Their preliminary experiments show that, in rat heart, Lx is without effect; however, Lxdiol suppresses the cardiac action potential, sodium current and transient outward current. This study will test the hypothesis that the mechanism of cardiotoxic effects of Lx is that Lx is metabolized by sEH to Lx-diol, causing its activation. Furthermore, the effects of Lx-diol are mediated by modification of kinetic properties of ion channels through intramembrane interactions with channel proteins. Specifically, the investigators will measure effects of Lx and Lx-diol on the cardiac action potential, sodium, calcium, and potassium channel currents and sodium potassium pump current. Effects on the action potential and membrane currents will be compared between rat, mouse, and guinea pig myocytes, as these species are known to have different intrinsic activities of sEH. Currents identified as being altered by either Lx-diol or Lx will be further characterized as to kinetic and voltage dependent properties to determine the mechanism by which currents are modified. Isolated adult cardiac myocytes will be used as the model system to test this hypothesis. Whole cell patch clamp techniques will be used to measure action potential and ionic currents in the isolated myocytes. Results of current measurements will be used to make predictions on effects in intact cardiac muscle that will be tested with papillary muscle experiments. Results of this study should demonstrate the role of sEH in toxic effects of Lx in which compounds (Lx or Lx-diol) is having a direct effect on the heart and, therefore, may be responsible for the heart failure seen both clinically and in the laboratory animals. Furthermore, this will provide new insights into the mechanisms responsible for this type of heart failure. Finally, they will begin to understand the mechanism of action of these compounds in altering electrophysiological properties of cardiac myocytes. This new evidence will provide a better understanding of these clinically important toxicants and may provide the basis for rationale treatment of these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CITRIC ACID CYCLE METABOLISM DURING CARDIAC SURGERY Principal Investigator & Institution: Jessen, Michael E.; Surgery; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 15-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from investigator's abstract) This investigator proposes a series of studies which will quantify substrate utilization in pathways designed to replete citric acid cycle intermediates lost during myocardial ischemia under conditions encountered during routine cardiac surgery. The proposed experiments will be conducted using an isolated perfused rat heart preparation and involve the use of labeled substrates and NMR spectroscopy. Oxidation of multiple citric acid substrates and anaplerosis will be studied under steady-state as well as during and after ischemia in the setting of various cardioplegic solutions. Specifically, the metabolic effects of cardioplegia will be studied, first in control hearts and then in hearts administered 1) warm continuous potassium cardioplegia, 2) an intracellular based cardioplegic solution, 3) low sodium and low potassium cardioplegia, 4) potassium cardioplegia with tetrodotoxin added to achieve polarized arrest, 5) the potassium channel opener pinacidil to achieve hyperpolarized arrest, and 6) washed and packed porcine erythrocytes to evaluate the effects of red blood cells on cellular metabolism. Once the metabolic effects of these interventions have been determined, the mechanisms by which potassium cardioplegia achieves suppression of fatty acid oxidation and stimulation of anaplerosis will be studied using substrates which cannot enter the TCA cycle via anaplerotic pathways. Studies will also
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be conducted in perfused hearts in which only pyruvate is labeled in order to detect the contribution of exogenous pyruvate. The next phase of the experiment includes evaluation of the metabolic effects of infusing potassium cardioplegia after ischemia. Finally, cardioplegic composition will be altered to include glutamate and aspartate. These studies will be designed to determine the linkage between metabolism and function and further eliminate mechanism of actions. It is anticipated that the findings will provide new information on the metabolic mechanisms that are important to preserving or enhancing cellular energy stores. This, in turn, should lead to improvements in cardioplegic solutions currently used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCHLEAR AND VESTIBULAR ION TRANSPORT Principal Investigator & Institution: Marcus, Daniel C.; Professor; Anatomy and Physiology; Kansas State University 2 Fairchild Hall Manhattan, Ks 665061103 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 31-DEC-2004 Summary: (provided by applicant): Meniere?s Disease is one of the pathological entities characterized by endolymphatic hydrops of the cochlear and vestibular labyrinths. Hydrops can result from an alteration of ion transport properties of the epithelial cells bordering the endolymphatic system. Little is known about the cellular basis of the pathologic processes involved because data are lacking from normal as well as pathological systems concerning active and passive mechanisms of secretion and absorption of ions. Endolymph is unique in that it is the only extracellular fluid in the body with a high potassium (K+) concentration and low sodium (Na+) and calcium (Ca2+) concentrations. It is proposed to study the ion transport processes responsible for fluxes of K+, Na+ and Ca2+ in the vestibular labyrinth and cochlea, specifically vestibular dark cells (VDC) and strial marginal cells (SMC), by further utilization of electrophysiologic techniques and in vitro preparations developed in this laboratory. Specific goals to be addressed by the proposed studies include determining a) the generator of endocochlear potential (EP) and cellular signaling pathways controlling K+ secretion by stria vascularis; b) cellular pathways mediating Ca2+ secretion and absorption; c) cellular pathways mediating control of Na+ and K+ absorption; and d) cellular pathways mediating control of Cl and HCO3 secretion and absorption. Specific parameters to be measured include transepithelial voltage and resistance with the micro-Ussing chamber, transepithelial fluxes of K+, Cl- and Ca2+ with ion- selective vibrating probes, and electrical properties of cell membranes with several configurations of the patch clamp technique. The completion of this project will further our understanding of the processes controlling secretion and absorption of medicallyimportant ions in the inner ear and may provide a foundation for the pharmacological management of inner ear disorders such as genetically-based syndromes and Meniere?s disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COCHLEAR HOMEOSTASIS Principal Investigator & Institution: Adams, Joe C.; Professor; Massachusetts Eye and Ear Infirmary 243 Charles St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The goal of the proposed work is to explore mechanisms of hearing loss induced by inflammatory cytokines in the cochlea. The work focused on the spiral ligament, because our recent work suggests that it 1) plays a critical role in cochlear fluid
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and ion homeostasis and 2) may be particularly susceptible to inflammatory processes. Type 1 fibrocytes are the most common cell type within the spiral ligament. They are part of a syncytium of cochlear supporting cells joined by intercellular connections called gap junctions. We have hypothesized that this gap junctional that this gap junctional system is essential for potassium ion recirculation from the organ of Corti to the stria vascularis and ultimately into endolymph, where a high potassium level is critical for normal high cell function. We have also found that type 1 fibrocytes contain high levels of the transcription factor NFkappaB, a protein that plays a key role in the acute phase inflammatory response of tissue to trauma or infections. In other tissues, inflammatory cytokines induced by NFkappaB can disrupt gap functional conductivity. Our working hypotheses is that inflammatory processes in the cochlea, arising from a wide array of disease states, induce cytokines in the spiral ligament, thereby blocking gap junctions between type 1 fibrocytes, depriving the stria vascularis of its potassium supply and producing profound sensorineural hearing loss. We will test this hypothesis by characterizing physiological and cytochemical responses of the cochlea following administration or induction of cytokines. We will measure changes in cochlear function by measuring evoke potentials and the endolymphatic potential and will use immunocytochemistry to document changes in cytochemical constituents of cochlear cells following the pharmacological experiments in order to determine the mechanisms underlying the cytokines' effects. The results may shed considerable light on the bases for sensorineural hearing loss in a variety of common, but poorly understood, otological disorders such as labyrinthitis, otosclerosis, genetic hearing losses involving gap junction proteins, and immune-mediated hearing loss. The proposed characterization of cytochemical substrates of inflammatory processes within the cochlea may help devise treatments or means of preventing hearing loss associated with these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPUTATIONAL STUDIES OF ION CHANNELS Principal Investigator & Institution: Roux, Benoit; Professor; Biochemistry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: Ion channels are highly specific membrane-scanning protein structures which facilitate and control the passage of ions across the cell membrane, our goal is to gain deeper insight into the structure and function of some important ion channels and lay the foundations for an understanding of the fundamental microscopic principles governing ion permeation using computational methods. We will study several aspects of the KcsA channel, the only channel selective for potassium ions for which the threedimensional (3d) structure was determined at atomic resolution. In addition, we will construct and refine 3d models of important K-channels. Using their homology t9 the known KcsA , and generate models of inhibiting toxins associated with the channel models using data from mutant cycles. These modeling projects are inter-related, e.g., the toxin/channel complexes are helpful for validating the channel models. Lastly, we will establish the range of microscopic validity of descriptions of ion permeation (Brownian dynamics, Nernst-Planck, Poisson-Nernst-Planck, Poisson- Boltzmann, and kinetic rate models) in relation to molecular dynamics stimulations and elucidate the importance of electrostatics on the charge specificity of porins. New software for simulating ion permeation will be developed and freely distributed for research and education. Our goal with these computations is to complement the (sometimes limited) information that is currently available from experiments and, ultimately, progress in our understanding of ion channels. In addition, the calculations are used to characterize
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various microscopic factors which cannot easily be accessed experimentally, but are essential for understanding the molecular determinants of channel function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOSOLIC REGULATION OF INNER EAR ION TRANSPORT Principal Investigator & Institution: Wangemann, a P.; Professor; Anatomy and Physiology; Kansas State University 2 Fairchild Hall Manhattan, Ks 665061103 Timing: Fiscal Year 2003; Project Start 01-JAN-1992; Project End 31-DEC-2007 Summary: (provided by applicant): Defects in potassium cycling, gap junction-mediated intercellular communication and cochlear metabolism are re-sponsible for the over whelming majority of hearing impairments This proposal is designed to further our under-standing of potassium cycling, by determining the role of connexins in potassium cycling, glutamate metabolism and the prevention of apoptosis and to determine whether a monocarboxylate shuttle contributes to meet the energetic needs of the cochlea. In detail, under Specific Aim 1, we will define the path of potassium cycling that leads from the hair cells in the organ of Corti to strial marginal cells in stria vascularis. Under Specific Aim 2, we will detelmine the subunit composition of the potassium channels KCNQ1 in strial marginal cells, KCNQ4 in outer hair cells and KCNJ10 in strial intermediate cells. These potassium channels are associated with hereditary forms of deafness KCNQ1 mediates potassium secretion into endolyinph, KCNQ4 mediates potassium release out of outer hair cells and KCNJ10 generates the endocochlear potentia. Each of these potassium channels is thus a major contributor to potassium cycling. Under Specific Aim 3, we will determine the role of connexins in glutamate metabolism and the prevention of apoptosis We hypothesize that glutamate metabolism in the organ of Corti is obligatorily dependent on connexin-mediated intracellular communication and that connexin hemichannels in supporting cells limit glutamate release from the inner hair cells. We will determine whether the capacity to metabolize glutamate is reduced by disruption of connexin-mediated intercellular communication and whether glutamate-induced metabolic stress causes opening of the mitochondrial permeability transition pore to initiate apoptosis. Finally, under Specific Aim 4, we propose to test the hypothesis that a monocarboxylate shuttle based in stria vascularis contributes to meet the metabolic needs of the organ of Corti. The completion of these studies will further our understanding of cochlear metabolism and homeostasis and provide a basic understanding of the molecular mechanisms that initiate the irreversible loss of sensory function in the inner ear. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF THE XENOPUS ACOUSTICO-VESTIBULAR SYSTEM Principal Investigator & Institution: Serrano, Elba E.; Associate Professor; Biology; New Mexico State University Las Cruces Las Cruces, Nm 880038001 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: The goal of this research is to gain an integrated view of the mechanisms that underlie development an, maturation of the sensory endorgans of the inner ear. Experiments will focus on the auditory and vestibular hair cells of the amphibian, Xenopus laevis. The proposed research will exploit the advantages that Xenopus offers as a classical system for developmental studies. The potassium channels of the inner ear will be a central subject of these investigations, and will be used to test hypotheses about hair cell development and differentiation. A major objective of this research is to
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establish the pattern of potassium channel gene expression in the developing inner ear. Electrophysiological methods (patch clamp) will be used to study ion channel function in dissociated hair cells. Molecular techniques will be used to clone ear potassium channels (RT-PCR, RACE, recombinant DNA) and will be combined with anatomical methods (in situ hybridization) to examine potassium channel mRNA expression in the ear. The specific aims of this research are to test the following hypotheses: (1) An outward potassium channel homologous to drkl is expressed in the Xenopus inner ear, (2) Xenopus saccular hair cell bundle morphology can be correlated with saccular hair cell electrical membrane properties, (3) The types of ion channels expressed in Xenopus saccular hair cells change as hair cells develop, (4) The properties of ion charmers differ between hair cells of the Xenopus sacculus, amphibian papilla, and basilar papilla. Experimental results are expected to advance fundamental understanding about the genetic basis of hair cell diversity, and about the genetic control of ear development. The long-term goal of this research is to lay the foundation for future studies that will determine how genes expressed in the ear are regulated during development and regeneration. Results of these investigations will provide essential knowledge that can be used to develop effective treatments for hearing loss such as that caused by trauma or genetic disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL CONTROL OF THE DIAPHRAGM AND UPPER AIRWAYS Principal Investigator & Institution: Cameron, William E.; Associate Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: (Adapted from the applicant's abstract): This proposal will characterize the postnatal development of the genioglossal and phrenic motoneurons, by correlating physiological changes in membrane conductance and spiking properties with changes in anatomy. The strength of respiratory muscle contraction is determined by the number of respiratory motoneurons activated and their rate of discharge. Both the order in which the neurons are activated and their discharge rates are a function of their resting conductance, that is, the number of membrane channels open at any given time. Most membrane channels are controlled by neurotransmitters and/or by the intrinsic electrical state of the cell membrane. The change in the balance of these two processes are most dramatic during postnatal development. The applicant is interested in these processes that occur in the two respiratory motoneurons that affect the performance of the diaphragm and genioglossus. Activation of these two muscles must be coordinated to move air into the lungs with the least effort; this may be particularly relevant to the pathophysiology of Sudden Infant Death Syndrome (SIDS). In the past period, the applicant established that glycine significantly contributed to the increase in resting membrane conductance that occurs at 3 weeks, and that these age-related increases in resting conductance result from an increase in the number of open potassium channels. The proposed studies will be performed on genioglossal and phrenic motoneurons in slice preparations of the rat brainstem and spinal cord. Visually identified motoneurons will be studied from four different age groups (1-2, 5-7, 13-15 and 19-22 days) with a combination of patch-clamp recording, three-dimensional neuronal reconstruction and immunocytochemical localization of certain receptors and ion channels. The application will: 1) examine the anatomy and physiology of glycine, GABA, and glutamate neurotransmitter systems at the four stages during postnatal development; 2) identify
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specific potassium channels that contribute to the increase in membrane conductance and spike characteristics; and 3) explore the intracellular pathways mediating the enhanced potassium conductance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DUAL GENE THERAPY FOR HEART FAILURE Principal Investigator & Institution: Nuss, H B.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JAN-2002 Summary: Heart failure is a multifactorial disease, having both electrical and contractile components. Downregulation of key potassium channels and concomitant prolongation and instability of repolarization, predispose the heart to arrhythmias. Meanwhile, downregulation of the sarcoplasmic reticulurn Ca2+ ATPase and concomitant calcium handling abnormalities contribute to depressed myocardial contractility. The electrical abnormalities and the contractile abnormalities are not mutually exclusive. Alterations in the control of membrane voltage will modulate the triggered release of Ca2+ from the sarcoplasmic reticulurn and, conversely, alterations in the intracellular calcium transient will influence membrane potential. It is the interplay between the electrical and contractile abnormalities of heart failure which compounds the complexity of abnormalities and confounds the design of successful treatments. Novel antiarrhythmic gene therapy based upon manipulation of a select K channel gene alone to decrease susceptibility to arrhythmias may lead to depressed contractility, which is already depressed in heart failure. Conversely, genetic manipulation of a SR Ca2+ ATPase protein alone, to amplify contractility, may create a proarrhythmic substrate in a failing heart which is already predisposed to fatal arrhythmic events. Thus, monogenic strategies, based upon selective overexpression of a single gene, may not suffice to correct heart failure abnormalities because of the interplay between excitation and contraction in cardiac muscle. This proposal seeks to offset abnormalities of tachycardia, pacing- induced heart failure in rabbits using combination gene therapy: overexpression of a select K channel gene and a SR Ca2+ ATPase gene in tandem. As a prelude we will test the hypotheses that gene therapy targeted to correct the electrical abnormalities alone or the calcium handling abnormalities alone will result in adverse conditions. The proposal focuses on potassium channels and SR Ca2+ ATPase's that are highly relevant to repolarization and contractility in the human heart failure. In vivo adenoviral mediated gene transfer, cellular and cardiac electrophysiology, and quantitative modeling will be used to investigate repolarization and calcium handling with the goal of correcting the electrical and contractile abnormalities in heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECTS OF EPOXYEICOSATRIENOIC ACIDS ON KATP CHANNEL Principal Investigator & Institution: Lee, Hon-Chi; Associate Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-JUL-2002 Summary: (Adapted from Applicant's Abstract): This proposal aims to explore the mechanisms of EET on KATP channels in heart. It is hypothesized that EETs are endogenous activators of KATP channels, and these actions are mediated through effects on ATP mediated inhibition of the Kir6.2 subunit. Molecular studies indicate that KATP channels consist of at least two types of subunits: the K channel subunit is referred to as KIR6.2, and the other subunit is a sulfonylurea receptor subunit (SUR).
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KIR6.2 is a member of the inward rectifier family of potassium channels. The SUR subunit is a member of the ATP binding cassette family of proteins and confers channel sensitivity to the sulfonylurea drugs. The functional channel is assumed to be an octomer consisting of four KIR6.2 subunits and four SUR subunits. The pancreatic beta cell KATP channel is composed of KIR6.2 and SUR1. The cardiac channel consists of KIR6.2 and SUR2A whereas the smooth muscle channel consists of KIR6.2 and SUR2B. EETs are potent endothelium-derived vasodilators that modulate vascular tone by way of enhancement of calcium-activated potassium channels in vascular smooth muscle. Cytochrome P450 monooxygenases convert arachidonic acid to 4 epoxyeicosatrienoic acid regioisomers, including 5,6-, 8,9-, 11,12- and 14,15- EET, as well as the 19 and 20 hydroxyecosatetronoic acids (HETE). Studies have shown that rat heart contains substantial amounts of endogenous EET, and 11, 12 EET has been shown to enhance the recovery of cardiac function following global ischemia. Under normal conditions, EETs are present at nM concentrations in plasma. During conditions of ischemia, formation of cellular EETs may be enhanced, thus EET's may play a role in the modulation of cardiac electrophysiology and vascular tone during ischemia. These hypotheses will be addressed by testing EETs on KATP channels using electrophysiology. EC50s for channel activation and the effects of ATP dependent inhibition will be evaluated. The structural determinants of EETs required in modulating channel function will be explored. The stereoisomers of EETs and as well as carbon chain elongated and shortened variants will be studied. The molecular mechanisms of EET will be examined using mutant Kir6.2 and SUR2A to determine the subunit requirements for modulation and to map the sites of action. The first specific aim is to determine the effects of the four EET isomers on KATP channels in rat ventricular myocytes using patch clamp methods. The effects of EETs on the pharmacological and electrophysiological properties of cardiac KATP channels will be investigated. It is hypothesized that EETs are endogenous activators of the channel. Although this may be the case, these experiments will not be able to determine whether EETs are endogenous activators by studying rat myocytes. Nevertheless, these experiments will provide an important characterization of the native channels. The second aim is to identify the structural determinants of EETs important for modulating KATP channels. The PI will investigate 5,6-, 8,9-, 11,12- and 14,15- EETs to explore the chemical requirements for activity. These experiments seem well thought out and should provide novel insights into the mechanisms of activation and specificity. A third aim will determine molecular mechanisms of EET effects on KATP channels by using cloned KIR6.2/SUR2A channels. The hypothesis is that EETs modulate the channel through altering the ATP interaction. It is believed from preliminary data that 11,12 EET caused a decrease in the ATP binding rate. This will be further explored through analysis of these actions on single KATP channels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENHANCED DRUG DELIVERY TO METASTATIC BRAIN TUMORS Principal Investigator & Institution: Black, Keith L.; Director; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Brain capillary endothelium and its contiguous cells, pericytes and astrocytes, are the structural and functional components of the bloodbrain barrier (BBB). Microvessels supplying brain tumors retain characteristics of the BBB, forming a blood-tumor barrier (BTB). While adequate delivery of drugs occurs to systemic tumors, the BTB limits delivery of antineoplastic agents to metastatic brain tumors. Drugs such as Herceptin, which is effective in treating metastatic tumors
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outside the brain have a high failure rate within the brain due to inadequate delivery across the BTB. The incidence of metastatic brain tumors is ten-fold higher than primary brain tumors. We have demonstrated that calcium-sensitive potassium (KCa) channel agonists selectively increase drug delivery across the BTB, and have postulated the biochemical mechanisms of this selective BTB permeability increase. We also have preliminary data suggesting that ATP-sensitive potassium (KATP) channel agonists selectively increase BTB permeability independent of KCa channels. These novel observations allow for a pharmacological mechanism for selectively increasing drug delivery across the BTB. This proposal will (a) further understand the mechanisms of KCa, and KATP channel activation in increasing BTB permeability and (b) optimize delivery of effective concentrations of drugs to metastatic breast and lung tumors in rats and humans via potassium channel-based mechanisms. We build on our data showing the ability of KCa channel agonists to selectively increase drug delivery across the BTB in rat glioma models and preliminary evidence suggesting that the BTB permeability increase may relate to over expression of KCa channels on glioma cells and tumor capillary endothelium. In this grant we will investigate 5 specific aims. Aim 1: To determine whether KCa and KATP channels are over expressed in metastatic brain tumor microvessels and tumor cells and whether increased expression correlates with increased permeability induced by KCa and KATP agonists. To test whether tumor cells can induce over expression of KCa or KATP channels on brain endothelial cells. Aim 2: To test by quantitative electron microscopy whether the mechanism of KATP channel agonist-induced BTB permeability increase is due to increased endothelial vesicular transport or opening of tight junctions. To test whether increased vesicle formation is correlated with changes in endothelial and tumor cell membrane potential. Aim 3: To investigate whether KCa and KATP channel agonists increase delivery of therapeutic monoclonal antibodies and chemotherapeutic drugs across the BTB into metastatic human breast and lung cancer in nude rats/mice. Aim 4: In nude rats/mice harboring metastatic breast and lung tumors we will investigate whether increased drug delivery across the BTB using KCa or KATP agonists results in inhibition of tumor growth, and whether survival is increased. Aim 5: The ability of a KATP channel agonist, minoxidil, to increase delivery of an anti-tumor drug to patients with brain tumors will be determined by LC-MS-MS in resected tumor tissues. This grant is responsive to the recent Brain Tumor PRG recommendation in 2001 to support studies to improve delivery of drugs across the BBB, particularly for metastatic brain tumors. Overall, these studies will further delineate the role of KCa and KATP channel activation as a mechanism for selective delivery of anti-cancer agents across the BTB and could potentially result in improved control of disease in patients with metastatic brain tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETHANOL ACTION THROUGH THE BK POTASSIUM CHANNEL Principal Investigator & Institution: Pierce-Shimomura, Jonathan T.; Ernest Gallo Clinic and Research Center 5858 Horton St, Ste 200 Emeryville, Ca 94608 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: The long-term goal of these studies is to molecularly characterize the action of important in vivo targets of ethanol in the nervous system that contribute to intoxication and addiction. Forward genetic screens in C. elegans have identified several key in vivo targets of ethanol that are required for intoxication. Most strikingly, the majority of the intoxicating effects of acute ethanol application in C. e/egans appear to be mediated via the ortholog of the human large-conductance potassium (BK) channel
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called SLO-1. Electrophysiological analyses found that ethanol potentiates the activity of the BK channel in vivo. The ethanol-induced increase in potassium efflux through the BK channel would cause a decrease in neuronal excitability, which may explain much of the depressive effects of ethanol on behavior. By combining the powerful genetic and molecular techniques of C. e/egans together with patch-clamp recording, the precise mechanism for how ethanol produces intoxication via the BK channel in vivo will be examined. This work will attempt to elucidate the site of ethanol action on the BK channel through site-directed and random mutagenesis of the channel. Studying mutants that are abnormally sensitive to ethanol may also identify proteins that interact with the BK-channel pathway to produce intoxication. Determination of the fundamental molecular mechanisms of ethanol action through the BK channel may provide a basis for a directed approach to design therapeutics to treat the detrimental effects of alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXCITABILITY, SYNAPTIC FUNCTION OF COCHLEAR HAIR CELLS Principal Investigator & Institution: Fuchs, Paul A.; Professor; Otolaryn & Head & Neck Surgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-DEC-1984; Project End 31-JAN-2006 Summary: adapted from applicant's abstract): This application calls for the continued study of excitability and synaptic function in mechanosensory hair cells of the chicken inner ear, especially concerning the role of voltage-gated ion channels. A new venture will involve extending these efforts to hair cells of the mouse cochlea. The regulated expression of voltage-gated calcium channels supports transmitter release, while associated calcium-activated (BK) potassium channels help to shape the receptor potential arising during transduction. The proposal seeks to understand the mechanisms that contribute to ion channel function and their role in synaptic transmission by the hair cell. The investigators will continue to probe the molecular composition of BK potassium channels in chick hair cells. They suggest that both alternative splicing of the alpha subunit, and modulation by accessory beta subunits contribute to the cell-specific kinetics of these channels. Thus, the investigators will seek further evidence for the differential distribution of beta subunits and of alpha subunits splice unit variants in the mature and developing cochlea of the chick. Single channel recording will be used to determine if the gating of native BK channels is consistent with the known influence of the beta subunit. Histological techniques and quantitative RTPCR will be used to chart the distribution and development of specific alpha and beta channel subunits. This application also proposes extend the studies to mammalian hair cells by making voltage clamp recordings in an excised preparation of the mouse cochlea. The investigators will examine the genesis of spontaneous activity in neonatal spiral ganglion neurons, characterize the biophysics and pharmacology of synaptic currents in afferent neurites at the bases of inner hair cells, quantify the relationship between hair cell calcium current and transmitter release, and determine how that varies with cochlear position and developmental age. These studies promise to further our understanding of the molecular physiology of cochlear hair cells. Further, the regulated expression of ion channels provides a window into the mechanisms that determine hair cell differentiation. The inclusion of the mouse model in this work tests the generality of these mechanisms among vertebrates, and provides an essential basis for the implementation of such studies in transgenic animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EXTRA-RENAL REGULATION OF POTASSIUM HOMEOSTASIS Principal Investigator & Institution: Mcdonough, Alicia A.; Professor; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): Extracellular fluid (ECF) +} must be maintained within a narrow range. If ECF +] falls too low (hypokalemia), cell membranes hyperpolarize, and if ECF +] increases too much (hyperkalemia) cell membranes depobrize, both disrupt normal electrical excitability and can have life threatening cardiac effects. Kidneys and muscle work in concert to maintain ECF ]. During hypokalemia muscle ICF K is redistributed to buffer the fall in ECF }. During hyperkalemia K+ is pumped into muscle ICF until renal adjustments can occur. These important muscle specific homeostatic processes are only beginning to be understood at the molecular level. Evidence supports the hypothesis that K loss from muscle during hypokalemia results from decreased active K+ influx mediated by sodium pump (Na,KATPase, NKA) inhibition, and that K+ uptake during hyperktilemia is mediated by sodium pump activation. Our lab has established that during low K+ diet abundance of NKA subunits are depressed in an isoform and muscle specific manner: 60-95 percent fall in a2, not a 1. Using a novel K+ clamp technique, we recently showed that early in K+ restriction, prior to fall in a2, there is a severe blunting of both insulin stimulated K+ uptake, and of insulin stimulated redistribution of NKA ct2 type pumps from endosomes to the plasma membrane (PM). Evidence is mounting that the bumetanide sensitive Na,K,2C1 cotransporter also accounts for a component of muscle K+ influx and, thus, could play a role in potassium homeostasis. The overall aims are to determine the molecular mechanisms responsible for tapping muscle K+ stores during hypokalemia, for clearing excess plasma +] into the ICF store after K+ restoration, and to understand how these processes are altered in a set of clinically relevant paradigms. The contribution of both Na,K-ATPase isoforms and NKCCI in both red oxidative white glycolytic muscle will be studied with a compartmental analysis approach in which the following are assessed: whole body K+ uptake, muscle specific K+ transport, subcellular distribution and activity of K+ transporters, and pool size regulation of K transporter protein and mRNA levels. Aim 1 will test the hypothesis that the shift of K+ to ECF during K restriction is mediated by decreased plasma membrane (PM) expression of both NKA a2 and NKCC1 coupled to resistance to insulin stimulated K+ uptake, and that this process is altered in uremia accompanying chronic renal failure. Aim 2 will test the hypothesis that thyroid hormone or dexamethasone, both of which increase NKA cx2 (and perhaps NKCC 1), alter extrarenal control of K+ horneostasis. Aim 3 will test the hypothesis that the uptake of K+ from ECF to ICF during K+ restoration (following K+ restriction) is mediated by normalizing surface expression of both NKA a2 and NKCC1. Accomplishing these aims will identify the cellular mechanisms responsible for tapping and repleting the muscle K+ reservoir, which will, ideally, suggest strategies to manipulate muscle K stores in clinical settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTION AND REGULATION OF CGMP GATED RENAL K+ CHANNELS Principal Investigator & Institution: Desir, Gary V.; Professor of Medicine; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-1994; Project End 31-MAR-2002
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Summary: (Adapted from the Applicant's Abstract): The kidney is the main organ involved in the long term regulation of total body potassium. Disorders of potassium balance occur frequently in patients who have hypertension, congestive heart failure, cirrhosis of the liver and renal dysfunction. Hypokalemia causes significant cardiovascular morbidity and mortality in patients treated with diuretics. Furthermore, abnormal regulation of K channels may play a role in the pathogenesis of hypertension. This laboratory is focused on the study of renal potassium channels. This work has let to the discovery of several novel K channel genes. One of these genes encode a cGMPactivated, K-selective channel (KCNA 10a) which is expressed in kidney, heart, muscle and blood vessels. KCNA10a has kinetic properties similar to those of the nitric oxide sensitive K channels detected in pulmonary artery smooth muscle cells. The work now proposed is an extension of the original proposal. The investigative team has recently succeeded in optimizing KCNA10a current expression in Xenopus oocytes and are now able to study its kinetic properties of the single channel level in detail. They will then determine if it is a hetero-multimeric protein and if its expression levels and/or kinetic properties are modulated by any of the live previously cloned a subunits. They will investigate the regulation of KCNA10a by cGMP and ask whether cGMP activates by binding to the cGMP-binding domain and/or via protein phosphorylation. Finally, a panel of high affinity polyclonal antibodies specific for the KCNA10a protein will be developed in order to examine its tissue distribution and membrane localization. The intent is that studies already carried out and those that are proposed in the current application will provide insight into the mechanisms by which K balance is maintained and should, therefore, have direct clinical applications. It is also hoped that the discovery of new molecular structures will expand the existing physiological framework of potassium homeostasis and will lead to the development of new therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION AND RENAL REGULATION X/K -ATPASE ISOFORMS Principal Investigator & Institution: Kone, Bruce C.; Director; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 01-APR-1994; Project End 31-JUL-2005 Summary: The H+ -K+ -ATPase alpha2 (HKalpha2) gene expressed in kidney and colon plays a critical role in the maintenance of body potassium and acid-base balance during chronic hypokalemia and chronic sodium depletion. The broad objectives of the proposed research are to identify the molecular mechanisms underlying the transcriptional regulation of this gene in the kidney and colon during these commonly encountered clinical conditions. Data are presented to indicate that the HKalpha2 gene is differentially regulated at the transcriptional level in the renal outer medulla and distal colon in response to chronic hypokalemia and states of aldosterone excess, respectively. The proposal examines the hypothesis that specific transcription factors selectively expressed or induced in these tissues interact with cis- regulatory elements to control HKalpha2 gene expression. The structural organization and precise chromosomal position of the murine HKalpha2 gene will be characterized. The selective effects of mineralocorticoids and glucocorticoids on HKalpha2 transcription in the distal colon and kidney will be analyzed to determine whether transcriptional induction is specific to the cognate nuclear receptors for these ligands. DNase I hypersensitivity assays and in vivo footprinting coupled with analysis of HKalpha2 regulatory regionreporter gene constructs will be used to map, at single nucleotide resolution, cellspecific promoter and enhancer elements in epithelial cell lines derived from the renal medullary collecting duct and distal colon under normal conditions and in response to
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low external K+ and aldosterone. Gel shift and supershift assays of nuclear extracts will be used to identify further the trans-acting factors responsible for HKalpha2 transcriptional control. The ability of the nuclear proteins to alter HKalpha2 promoter/enhancer in trans will be tested in coexpression experiments. Studies in transgenic mice will test whether candidate regulatory elements identified in vitro faithfully mirror the tissue expression and responses to chronic K+ - or Na+-deprivation, and aldosterone excess of the endogenous HKalpha2 gene. The results of these studies should provide important molecular insights into the regulation of the HKalpha2 gene and its unique roles in renal and intestinal cell biology and pathobiology. The proposed studies should also yield fundamental information that can be more broadly applied to the Na+-K+-ATPase/H+-K+-ATPase multi-gene family, the molecular basis for tissuespecific gene regulation, and the molecular mechanisms responsible for selective steroid action on target genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOMICS OF POTASSIUM CHANNELS IN C ELEGANS Principal Investigator & Institution: Salkoff, Lawrence B.; Professor; Anatomy and Neurobiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2003 Summary: This is a proposal to undertake a comprehensive study that will reveal the structure, expression patterns, and basic functional properties of all potassium channels in C. elegans. The project will provide the first glimpse of the entire K channel set in one animal, without favoring any cell, tissue type or abundance class, revealing aspects of genomic organization that are not discernible without the complete gene sequences. Initially, all sequence information revealed by the C. elegans genomic project at Washington University will be compiled, and then the expression patterns of individual K channels will be determined. Because there are an estimated 100 potassium channels in an organism with only 302 neurons, many of these channels may be under coordinated regulation for expression; this may be required for complex electrical behavior. This study may lead to a profile not only of structure an functional properties, but also tissue distribution and amount and timing of expression. These data may serve as a model for interpreting the human genome sequence data, and may also lead to clinical applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLIAL-NEURONAL INTERACTIONS IN THE RETINA Principal Investigator & Institution: Newman, Eric A.; Professor; Neuroscience; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-JUL-1990; Project End 31-MAR-2005 Summary: (Verbatim from applicant's abstract): The long-term objective of this project is to determine the functions of glial cells (Muller cells and astrocytes) in the mammalian retina. It is widely recognized that glial cells have important support functions in the retina, including uptake of neurotransmitters and regulation of extracellular potassium and pH. The role of glial cells in direct modulation of neuronal activity is not yet understood, however. In the preceding project period, we demonstrated that intercellular Ca2+ waves can be propagated through glial cells in the rat retina and that these glial Ca2+ waves modulate spike activity in neighboring neurons. In the proposed project period, we will extend our studies of glial modulation of neuronal activity and explore additional aspects of glial Ca2+ signaling with the goal of determining the
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significance of these interactions in vivo. The specific aims for the project period are: (1) to identify natural stimuli that elicit Ca2+ signals in retinal glial cells; the hypotheses to be tested are that: (a) chemicals released under normal or pathological conditions evoke glial Ca2+ increases, and (b) light stimulation evokes glial Ca2+ increases; (2) to test the hypothesis that spontaneous Ca2+ oscillations in glial cells modulate the activity of neighboring neurons, using regression analysis to correlate neuronal spike activity and membrane potential with Ca2+ levels in adjacent glial cells displaying spontaneous Ca2+ oscillations; (3) to characterize mechanisms of glial cell modulation of neuronal activity; the hypotheses to be tested are that: (a) excitatory neuronal modulation is mediated by release of glutamate from glial cells onto neurons, and (b) inhibitory modulation is mediated indirectly by glial activation of inhibitory amacrine cells; (4) to elucidate the mechanism by which Ca2+ waves are propagated in retinal glial cells; the hypothesis to be tested is that wave propagation is mediated by the release of ATP, which functions as an extracellular messenger; and (5) to characterize physiological changes in retinal glial cells elicited by propagation of Ca2+ waves; the hypotheses to be tested are that: (a) Ca2+ increases modulate inward rectifier potassium and Ca2+dependent potassium conductances, and (b) Ca2+ increases generate intracellular pH variations in retinal glial cells. Glial cells have been implicated in many types of retinal pathology, including diabetic retinopathy, glaucoma, and macular degeneration. Knowledge of the basic physiological properties of retinal glial cells and their interactions with retinal neurons will add to our understanding of how these cells contribute to retinal pathology. The research outlined in this application will provide significant progress towards this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: H,K,ATPASE FUNCTION IN POTASSIUM HOMEOSTASIS Principal Investigator & Institution: Wingo, Charles S.; Professor of Medicine and Physiology; Medicine; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2004 Summary: The long-range goal of this research is to examine the role of H,K-ATPases in potassium homeostasis and to determine how these ion-motive pumps are regulated by ion channels. H,K-ATPases are important for renal potassium conservation, but it is now apparent that the kidney possesses several different H,K-ATPase enzymatic activities which likely reflect the presence of multiple gene products. Experiments in Specific Aim 1 will determine the molecular identities of the H,K-ATPase subunit isoforms that are responsible for specific enzymatic activities, and for potassium and proton flux in discrete nephron segments, by the study of animals with targeted gene disruption of the H,K-ATPase HK-alpha-1, HK-alpha-2, or HK-beta genes. Experiments in Specific Aim 2 will examine whether knockout of HK-alpha-1, HK-alpha-2, or HKbeta subunits affects the normal anatomy of the kidney or the morphological response to potassium depletion. Experiments in Specific Aim 3 will characterize fully the newly discovered potassium-permeable ion channels that are present at the apical membrane of the inner stripe of the outer medullary collecting duct (OMCD), and the cell types that contain these channels. These channels exhibit novel properties since they appear to be stimulated by cellular acidification whereas most potassium channels are inhibited by acidosis. The proposed experiments are intended to establish the contribution of each of these genes to an important adaptive response (potassium depletion), the compensatory renal response to the disruption of these genes, and whether these genes are involved in the normal morphology of the kidney or its response to potassium depletion. Since accruing evidence indicates that modest potassium depletion causes or contributes to
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systemic arterial hypertension, and may contribute to chronic renal insufficiency, these studies area expected to contribute to our understanding of the role of potassium depletion as a risk factor for both renal and cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION
HETEROGENEITY
IN
CARDIAC
POTASSIUM
CHANNEL
Principal Investigator & Institution: Roden, Dan M.; Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 31-JUL-2002 Summary: The electrophysiologic behavior of the heart is highly heterogeneous. It has been, and continues to be, the goal of this Program to define mechanisms underlying this heterogeneity. In the last period of support, substantial progress has been made toward this goal. The present renewal application has been restructured to focus specifically on cardiac potassium channels, testing the overall working hypothesis that variability in expression or function of these channels is an important determinant of heterogenous repolarization both in health and in disease. The studies proposed will incorporate both conventional molecular and electrophysiologic techniques as well as new techniques in which Program investigators and collaborators have developed considerable expertise in the last period of support; these include generation of genetically-modified mice, in situ hybridization, the molecular genetics of cardiac ion channels, and spin labeling/EPR technology. In each Project, preliminary data that attest to feasibility are presented, and specific hypotheses relating to the mechanisms underlying heterogeneous function or expression of cardiac K plus channels are proposed for testing. The experimental models include wild-type and mutant channels in heterologous expression systems, the use of genetically-modified animals, and studies in human subjects. The focus of the central theme of cardiac potassium channels allows a high degree of scientific interchange among Projects; this includes the use of shared reagents, as well as the likelihood that results in one Project influence the scientific direction in others. Dysfunction of cardiac potassium channels is increasingly recognized to play a role in the genesis of cardiac arrhythmias. The studies proposed in this Program will help elucidate mechanisms underlying this dysfunction, and therefore point to novel approaches to therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN SPERM ZONA ACCEPTOR: ENVIRONMENTAL EFFECTS Principal Investigator & Institution: Benoff, Susan H.; Associate Professor; North Shore University Hospital 300 Community Dr Manhasset, Ny 11030 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 31-JUL-2006 Summary: (provided by applicant): We focus on developing an understanding of toxic metal action in the human testis. A male factor is present about 60% of infertile couples, but underlying molecular mechanisms are largely uncharacterized. Exciting results from our current work hints at one mechanism. Lead levels were elevated markedly in testes and seminal plasma (in 25% of males in four independent populations). High lead correlated with expression of particular potassium and calcium ion channel isofomis, with poor sperm-fertilization-potential biomarkers and low fertility by IVF, artificial insemination and coitus. A significant fraction of subjects studied longitudinally switched from high lead states to low lead states, with simultaneous conversion of biomarkers from infertile to fertile and switch in potassium channel isoform expression.
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This suggested lead epigerietically modified testicular gene expression (at the levels of transcription and mRNA splicing) and that potassium channel isoforms could be developed as biomarkers for lead exposure. A preliminary DNA microarray study of a lead-treated "lead-resistant" rat strain identified many lead-affected genes as being involved in calcium-mediated induction of apoptosis, including a potassium channel. Supported by current somatic cell apoptosis mechanisms, this prompted our hypothesis that lead exposures produce male infertility by altering calcium homeostatsis, and a related detailed mechanism of lead action. These will be tested in a lead-treated leadsensitive" rat strain and in humans. We will use microarrays to probe in rats for affected testicular genes with CAMP response elements and other genes involved in calcium/calmodulin-dependent protein kinase IV signaling. Controls include metal testing by atomic absorption, TUNEL estimates of apoptosis, cell type levels by histology and by cell-type-specific mRNA levels, and protein expression by Westerns. Comparison with the "lead-resistant" strain should identify lead-sensitivity" genes. We will probe for the same genes in a human clinical population, with similar controls. We will also probe for genes co-regulated with the potassium channel above. Results will test several specific steps in our proposed mechanism: verifying, negating or modifying it. Because microarrays cannot detect differential calcium channel splicing events correlated with lead effects upon human testes, this gene and other calcium transporters will be studied by immunocytochemistry, RT in situ PCR and real-time PCR. Outcome is test of hypothesis, and possible mechanism explaining infertility associated with low sperm counts or idiopathic male infertility, tools for diagnosis, and hope for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IGF-1 & RAS IN DEVELOPMENT /REGRESSION OF HYPERTROPHY Principal Investigator & Institution: Haddad, Georges E.; Assistant Professor; Howard University 2400 6Th St Nw Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-JUL-2006 Summary: Cardiac hypertrophy is a pathological state that can lead to heart failure. More than the quarter of US adult American population lives , whereby more than half of these cases are associated with cardiac hypertrophy. A universal electrophysiological finding in ventricular cells of hypertrophied heart is prolonged on the action potential duration (APD), which facilitates the propagation of re-entry arrhythmias and heart failure. The role of different ionic currents responsible for this APD lengthening is still debatable; mainly due to the fact and electrophysiological alterations are dependent on the etiology stage and model of hypertrophy and species. On the other hand, the reninangiotensin system plays an important role in the regulation of cardiovascular tone and hypertrophy through its vasoactive component, angiotensin II (ANG II) mainly via its non-tyrosine kinase G-protein AT1 receptors. However, it is more evident that ANG II mitogenic effects are mediated essentially by the tyrosine kinase IGF-1 receptors through a cross talk with activated AT1 receptors. This proposal is intended to elucidate the modulation by ANG II and IGF-1 of potassium (IK1 and IK-ATP) and calcium (Ica,L) channels during the development and regression phases by (angiotensinconverting enzyme inhibitor (ACE-I) or AT1-antagonist treatment) of cardiac hypertrophy in the adult rat. The patch-clamp technique will be used to study channel activity, while the intracellular imaging technique with Fura-II will be used to monitor changes in intracellular calcium handling in isolated ventricular myocytes. Changes at the membrane level will be correlated to ANG II- and IGF-1-induced changes at 2nd messenger level (PKA, PKC, PI-3 kinase, and downstream tyrosine kinase and MAP kinase) during cardiac hypertrophy and after its regression by ACE-I or AT1-antagonist.
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The mitogenic effects of ANG II and its cross talk with IGF-1 signal transduction will be evaluated in association with the electrophysiological changes during both phases. Therefore, the effects of ANG II on Ica, L and [Ca2+]i as well as potassium currents (IK1 and IK-ATP) will be compared in the presence of varying IGF-1 concentrations. Thus, this project will identify and evaluate the signal transduction pathways mediating both ANG II and IGF-1 effects and the importance of the cross talk during the development and regression of cardiac hypertrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INACTIVATION OF NEURONAL KV4 POTASSIUM CHANNELS Principal Investigator & Institution: Covarrubias, Manuel L.; Assistant Professor; Pathology, Anat/Cell Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2003; Project Start 15-DEC-1993; Project End 31-JAN-2007 Summary: (provided by applicant): The long-term goal of this project is to understand the molecular mechanisms that control inactivation of neuronal Kv4 potassium channels. These potassium channels mediate the transient potassium current that is necessary for coding, integration and amplification of electrical signals in the nervous system. Kv4 channels probably utilize novel mechanisms of inactivation, which are distinct from those better known in Shaker potassium channels. Discoveries made during the last funding period are beginning to shed light on the physiological basis of Kv4 inactivation and how novel subunits shape this process. The specific aims for the next funding period are: (1) To probe conformational changes underlying a prominent pathway of inactivation in Kv4 channels; (2) To map the cytoplasmic moving regions controlling inactivation gating of Kv4 channels; (3) To investigate the molecular mechanisms underlying remodeling of Kv4 inactivation by Kv4-specific neuronal calcium sensors (KChlPs);(4) To investigate the molecular determinants of a KChIP domain with unique modulatory properties. Recombinant DNA technology, patchclamp electrophysiology and thiol-specific reagents are applied to study inactivation of Kv4 channels expressed in heterologous expression systems (e.g., Xenopus oocytes or mammalian cells). Nuclear magnetic resonance (NMR) is applied to solve the structure of a putative inactivation domain in Kv4 channels. By investigating these aims, this project may gain insights into the molecular basis of brain functions that depend on the precise timing of electrical signaling, a domain where inactivation gating of Kv4 channels plays its most significant role. Specific areas that may benefit from this research include studies of associative learning and epilepsy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ION CHANNEL FUNCTION IN AUDITORY & VESTIBULAR HAIR CELLS Principal Investigator & Institution: Holt, Jeffrey R.; Assistant Professor; Neuroscience; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2006 Summary: The studies proposed here focus on the function of KCNQ potassium channels in the sensory hair cells of the auditory and vestibular systems. Mutations in four of the five members of this newly discovered class of voltage-gated ion channels cause inherited human diseases. At least three of these proteins are expressed in the auditory and vestibular periphery: KCNQ1, 3 and 4. Mutations in two of them, KCNQ1 and 4, cause severe auditory dysfunction. Although the etiologies of these inherited
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conditions are not well understood, the profound sensory deficits imply an important role for KNCQ proteins in normal auditory function. This project has two main goals. This first goal is to correlate expression of KCNQ potassium channels with the normal physiology of auditory and vestibular hair cells. This will provide new insight into how mutations in the KCNQ gene family lead to pathological states. The second goal is to investigate the role of KCNQ channels in synaptic transmission in the vestibular periphery. Specifically, we will test the hypothesis that the type I hair cell afferent synapse utilizes a novel form of K+-dependent neurotransmission. To address these questions we have devised a common strategy. A mutation within the pore-forming region of these potassium channels acts in a dominant manner to block conduction. Using virus-mediated gene transfer we will express mutant KCNQ genes in cells of organotypic cultures from the mouse auditory and vestibular organs. Expression of mutant KCNQ genes in normal cells will suppress the activity of wildtype KCNQ subunits. To assay for disrupted function we will characterize the electrophysiological properties of infected cells, identified by coexpression of green fluorescent protein, and neighboring uninfected control cells. Thus, in a specific and controlled manner we will link a molecular identity with its physiologic correlate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ITO IN DOGS WITH INHERITED VENTRICULAR ARRHYTHMIAS Principal Investigator & Institution: Kornreich, Bruce G.; Molecular Medicine; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001; Project Start 15-JUN-2001; Project End 31-MAY-2006 Summary: Abnormalities of ventricular repolarization have been identified in a number of cardiac disease states and may predispose to malignant or fatal ventricular arrhythmias. The transient outward potassium current, I- to, is an important determinant of ventricular repolarization. The potassium channel isoform responsible for I-to varies between species. Kv1.4, Kv1.5, Kv4.2, and Kv4.3 have been identified as contributors to ventricular repolarization in various species, with Kv1.4, Kv4.2, and Kv4.3 representing the most likely contributors to I-to in canine cardiac myocytes. Decreased I-to density has been found in several pathologic states including myocardial hypertrophy, terminal heart failure, and acute Trypanosoma cruzi infection, and prolonged ventricular repolarization may increase the morbidity and mortality of these conditions. Moise and collaborators have previously reported a line of German Shepherd dogs with inherited ventricular arrhythmias and sudden death. Affected dogs have a decreased sympathetic innervation of the left ventricle and decreased left ventricular I-to density. Norepinephrine application rescues I-to in myocytes isolated from affected regions in these dogs, suggesting that the decreased I-to may result from a loss of the trophic influence of the sympathetic nervous system during development. Nerve growth factor and enkephalins have been shown to promote growth and survival of central and peripheral neurons. Using whole cell patch clamp recording ribonuclease protection assays, and Western blot techniques, we will address the following questions: (1) Is decreased NGF and ppENK expression responsible for the abnormal peripheral sympathetic innervation in the hearts of affected dogs? (2) Which potassium channels (Kv1.4, Kv1.5, Kv4.2, and Kv4.3) are responsible for I-to in affected dogs? Is the decreased expression of one or a combination of these channel isoforms responsible for deceased I-to in affected dogs? Is the increased expression of one or a combination of these isoforms responsible for NE mediated restoration of I-to in affected dogs?, and (3) Is the restoration of I-to by NE in the hearts of affected dogs mediated by alpha or beta adrenergic receptors and their associated second messenger cascades? The scientific
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training obtained while performing this research in a vital and supportive intellectual environment will provide valuable theoretical and technical experience for the applicant to expand upon his clinical and basic scientific experience to achieve his goal of a link between the basic scientific study of membrane bound ion channels/receptors and clinical cardiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: K+ CHANNEL EXPRESSION ON MYELIN REACTIVE EFFECTOR T CELL Principal Investigator & Institution: Calabresi, Peter A.; Associate Professor; Neurology and Neurosurgery; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-JUL-2000; Project End 31-AUG-2007 Summary: (provided by applicant): Strategies designed to specifically suppress the function of myelin-reactive T cells are an objective of pharmacological therapy in multiple sclerosis (MS). We have focused our studies on identifying markers of costimulation independent memory cells that might be amenable to therapeutic intervention. In the last two years, we have demonstrated that two chemokine receptors, CXCR3 and CXCR6, are highly expressed on Th1 myelin specific effector T cells. We have also determined that the loss of the lymph node homing chemokine receptor, CCR7, is an excellent marker of conversion of myelin reactive T cell lines from an early effector state CD45RA-/CCR7+) to an effector memory state (TEM=CD45RA-/CCR7-), and that these TEM are synonymous with the previously described costimulation independent T cells in MS. In a recent collaboration, we have now identified a voltagegated potassium (K+) channel, Kv1.3, which is specifically and highly expressed on chronically differentiated TEM. We have demonstrated that the myelin reactive Kv1.3highTEM are present in MS patients and not in controls. We will now characterize the specificity of Kv1.3 expression on effector and regulatory subtypes of CD4 and CD8 T cells, and test the hypothesis that specific Kv1.3 inhibitors will selectively suppress TEM, without compromising immediate immune responses or regulatory T cells. We will examine these hypotheses through the following specific aims: Specific Aim 1. To determine the peptide specificity of the myelin reactive TEM (CCR7-, Kv1.3highlKCa1low). Specific Aim 2. To determine whether CD8 myelin specific T cells from MS patients have the TEM (CCR7-, Kv1.3highlKCa1 low) phenotype as compared to controls using class I tetramers. Specific Aim 3. To evaluate the effects of Kv1.3 antagonists on TEM function. Specific Aim 4. To determine the expression and function of Kv1.3 on myeloid lineage cells in vitro and in the inflammatory infiltrate of MS brain tissue. The results from these K+ channel studies on human immune cells will have broad implications for defining the potential role of K+ channel blockers in specifically targeting effector cells, and could lead to novel treatment strategies for MS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: K-DEPENDENT NA/CA EXCHANGE IN HUMAN PLATELETS Principal Investigator & Institution: Kimura, Masayuki; Pediatrics; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Recent work has demonstrated that the platelet Na/Ca exchanger (NCX) in human beings is identical to the retinal rod NCX. This exchanger plays an important role in regulating platelet Ca stores and it is driven not only by the Na electrochemical gradient but also by the K electrochemical gradient across the platelet plasma
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membrane. In addition, platelets express the alpha3 isoform of the Na-pump, an isoform with a heightened sensitivity to cardiac glycosides. These features of the platelet ion transport strongly link platelet Ca metabolism to fluctuations in systemic Na and K homeostasis and to the activity of the platelet Na-pump. At the core of this project is the hypothesis that the link between platelet Ca homeostasis and systemic Na/K regulation explains some cardiovascular effects of high Na and high K intakes that are independent of the effects of Na and K intakes on blood pressure. Three specific aims will explore this hypothesis. Specific Aim 1 will decipher the physiological and molecular characteristics of the Na-pump in human platelets, focusing on the alpha3 subunit isoform in these cells and its sensitivity to cardiac glycosides. The results will provide a better appreciation of the link between platelet NCX and the Na-pump. Specific Aim 2 will test the hypothesis that a high Na intake raises cytosolic Na, lowers cytosolic K, and inhibits the NCX to increase platelet Ca stores and platelet reactivity in human beings. Specific Aim 3 will test the hypothesis that a high K intake lowers cytosolic Na, raises cytosolic K and stimulates platelet NCX activity to diminish platelet Ca stores and platelet reactivity in human beings. Findings of this project might identify previously unknown cardiovascular effects of dietary Na and K, thereby revealing a new dimension of 'salt sensitivity' in human beings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEASURING FLUORESCENCE
ION
CHANNEL
PORE
DYNAMICS
WITH
Principal Investigator & Institution: Korn, Stephen J.; Professor; Physiology and Neurobiology; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, Ct 06269 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2003 Summary: (provided by applicant): Voltage-activated potassium channels serve several critical functions in all excitable cells (brain, heart, endocrine and muscle), including repolarization of action potentials and control of rhythmic firing patterns. Channel properties that control the functional outcome of channel activity include current magnitude and the rate of channel gating events (activation, inactivation and deactivation). The functionally rich outer vestibule/selectivity filter region of the potassium channel pore has been considered to have just a single conformation in the open state, and have little or no role in the modulation of open channel function. Recently, we described a novel mechanism by which current magnitude, activation rate and inactivation rate, as well as both internal and external channel pharmacology, are modulated by relevant changes in external potassium concentration. We demonstrated that changes in these channel properties, which can be substantial, result from a previously unknown type of conformational change that occurs in the outer vestibule of the pore. Furthermore, this conformational change in the outer vestibule is observed only in channels that display properties consistent with a "structurally flexible" selectivity filter region of the pore. These results suggest the possibility that, in contrast to what has been previously believed, the permeation pathway in some ion channels has a significant degree of "structural flexibility," and that this "flexibility" can markedly affect open channel function. Neither the nature of the conformational change, nor a detailed understanding of how it is regulated, can be obtained solely with electrophysiological techniques. The goal of this application is to integrate two sophisticated fluorescence techniques, fluorescence quenching and fluorescence resonance energy transfer (FRET), with patch clamp electrophysiology in our lab. This will allow us to directly examine the nature of the conformational change, and the mechanisms that control the conformational change. It will also allow us to test the
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fundamentally novel hypothesis that differences in "structural flexibility" of the permeation pathway underlie, in part, differences in functional regulation of closely related ion channels. The ability to incorporate this technology into our research will provide a new and enhanced approach for our study of ion channel mechanisms, and will allow us to collect preliminary data necessary for subsequent funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF UTERINE VASCULAR ADAPTATION IN PREGNANCY Principal Investigator & Institution: Gokina, Natalia I.; Obstetrics and Gynecology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 04-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Normal pregnancy is characterized by a remarkable enhancement of uterine blood flow due to vasodilation and growth and remodeling of uterine vasculature that is associated with an increased uterine reactivity to vasoconstrictors. The long-term goal of this proposal is to understand the causes and cellular mechanisms underlying the modulation of uterine vascular contractility during gestation, with a specific focus on the role of ion channels in endothelial and vascular smooth muscle cells. Our central hypothesis is that pregnancy down- regulates the delayed rectifier and Ca2+-activated potassium channels with a resultant increase in Ca 2+ influx and smooth muscle contractility. Enhanced Ca 2+ sensitization of contractile process is a synergistical mechanism. Pregnancy-induced up-regulation of PKC and RhoA is proposed as a common regulatory mechanism for enhanced Ca 2+ sensitization and inhibition of K+ channel function. These adaptive changes are counteracted by increased Ca2+-dependent production of endothelium-derived NO and EDHF. Furthermore, we suggest that the effects of pregnancy are highly localized by the side of placentation and are mediated by estrogen. Specific Aim 1 will determine the mechanisms that regulate a steady state global [Ca2+]_ in smooth muscle of uterine resistance arteries, and their modulation in pregnancy. The role of PKC and RhoA in regulation of Ca 2+ sensitization and ion channel function will be studied. Specific Aim 2 will explore the mechanisms by which NO and EDHF mediates the effects of pregnancy on uterine arterial contractility with a specific focus on the role of endothelial intracellular Ca 2+ and small conductance Ca 2+-activated potassium channels. Specific Aim 3 will test the role of local vs. systemic factors, and of estrogen in mediating the effects of pregnancy on uterine artery function. The three Specific aims will integrate the physiological function (regulation of arterial diameter) with intracellular (Ca 2+ signaling, Ca 2+ sensitivity and ion channel function) and molecular (PKC and RhoA) mechanisms and will be accomplished by direct measurements of arterial diameter, intracellular Ca, membrane potential, expression and distribution of PKC and RhoA, and ion currents in endothelial and smooth muscle cells. The proposed study will provide new insights into cellular and molecular mechanisms mediating the effects of pregnancy and estrogen on uterine blood flow and significantly deepen the understanding how these mechanisms are altered in pregnancy-induced hypertension and preeclampsia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MEMBRANE PROCESSES MEDIATING K+ SECRETION Principal Investigator & Institution: Palmer, Lawrence G.; Professor; Physiology and Biophysics; Weill Medical College of Cornell Univ New York, Ny 10021
32
Potassium
Timing: Fiscal Year 2001; Project Start 01-MAR-1981; Project End 31-JAN-2002 Summary: (Adapted from the Applicant's Abstract): The kidney maintains the appropriate amounts of potassium in the body by matching the amounts of salt excreted to those which are in the diet. The final regulation of K+ balance is thought to occur in the collecting tubule. Here, the amount of K+ secreted or absorbed depends on the activities of apical K+ channels. Previous work showed that when dietary K+ is high, the density of apical K+ channels is increased through a mechanism which is independent of aldosterone. In the proposed research they will explore this regulatory process further, focusing on the systems controlling the K+ channels. Experimental studies will involve the use of a combination of electrophysiological and molecular biological approaches. They will explore in detail the relationship between K+ channel density and dietaryes, they will examine the time course and load dependence of the upregulation of conducting K+ channel density. They will also test whether the channels are downregulated in animals on a K+-restricted diet. The principal investigator will test the hypothesis that increased levels of mRNA underly the control of the density of conducting channels using quantitative in situ hybridization techniques. The principal investigator will use antibodies raised against the K+ channel to map the sites of apical K+ channel expression and to assess the role of changes in the amount of K+ channel protein in the regulatory process. He will also explore the relationship between the longterm regulation of the K+ channels with more short-term processes. These will include both regulation through cAMP and PKA, and channel activation by acute elevation of extracellular K+. The biophysical and molecular basis for the latter effect will also be studied using the Xenopus oocyte expression system. This research should help illuminate how K+ transport by the distal nephron is regulated during health (changes in diet) and disease (e.g. renal insufficiency). It will also help to clarify how Na+ and K+ transport can be regulated separately in the collecting tubule to maintain blood volume and pressure as well as plasma K+ concentration within narrow limits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMBRANE TRAFFICKING AND CHANNEL ABUNDANCE Principal Investigator & Institution: Jan, Lily Y.; Professor and Hhmi Investigator; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2006 Summary: (Provided by Applicant): For signaling to proceed normally in the nervous system, there has to be the right number of the right type of ion channels and transmitter receptors on the neuronal membrane. What kind of quality control machinery can ensure the proper assembly of these membrane protein complexes? How does a cell control the number of channels and receptors on its cell membrane? We have found a novel quality control mechanism that curtails the trafficking of inadequately assembled membrane protein complexes from the endoplasmic reticulum (ER) to the cell membrane. This ensures surface expression of fully assembled ATP-sensitive potassium (K-ATP channels with four Kir6.2 and four SUR subunits, and of properly assembled, heterodimeric GABA-B receptors that can functionally couple to the G protein-activated inwardly rectifying potassium (GIRK or Kir3) channels. The ER retention/retrieval signals in the K-ATP channels also limit the number of these channels on the cell surface. How general might be the use of ER retention/retrieval in the quality control of membrane protein complexes? Does the cell regulate other steps of membrane trafficking to control the number and type of ion channels and transmitter receptors? We have developed new methods to test the hypothesis that the numbers of different potassium channels are subjected to different membrane trafficking
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regulations. The examples to be used in our study are potassium channels that mediate slow synaptic potentials, control neuronal excitability, and potentially protect central neurons under stress. Mutations of potassium channel proteins are known to cause ataxia, epilepsy, deafness, arrhythmia, hypertension, and unchecked insulin release leading to hypoglycemia. Indeed, human epilepsy could result from mutations that reduce the M-type potassium channel activity by only 25 percent. And some of the disease-causing mutations alter the amount of functional potassium channels on the cell membrane. Our goal is to achieve better understanding as to how membrane trafficking regulates channel number and type. This may help us appreciate in the long run how regulation of membrane trafficking might contribute to synaptic plasticity, and whether malfunctions of this process contribute to mental and neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODIFIERS OF POTASSIUM CHANNEL FUNCTION AND EXPRESSION Principal Investigator & Institution: Robertson, Gail A.; Associate Professor; Physiology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The human ether-a-go-go-related gene (HERG) encodes an ion channel subunit underlying IKr, a potassium current required for the normal repolarization of ventricular cells in the human heart. More than 90 inherited mutations in HERG cause Long QT Syndrome (LQTS), a leading cause of sudden cardiac death. Some mutations alter gating, but more disrupt trafficking. Because the subunit composition of HERG is uncertain, and the mechanisms underlying HERG biogenesis, processing and targeting to the membrane are unknown, we carried out a yeast two-hybrid screen to identify proteins that interact with HERG. Using the carboxy terminus as bait to screen a human heart library, we isolated five genes encoding HERGinteracting proteins ("HIPs"). Two of these proteins have been previously identified: Tara, an actin-binding protein, and GM 130, a peripheral membrane protein of the Golgi apparatus. Little is known about the function of either. Tara co-localizes with HERG to a region in rat cardiac myocytes corresponding to the T-tubules, as determined by confocal immunocytochemistry. Consistent with a stabilizing role at the membrane, Tara enhances expression in HERG when co-expressed in Xenopus oocytes. GM 130 specifically localizes to the Golgi, where a prominent HERG signal is also observed. In contrast to Tara, GM130 suppresses HERG signal in oocytes. Deletion mapping in binary yeast two-hybrid assays reveals that the C terminus contains distinct domains with which the HIPs selectively interact. Certain LQT2 (HERG) mutations selectively disrupt interactions with only two of the proteins. Three of the proteins, Tara, H17 and H3, interact with each other, implying that they function as an interactive complex. Of the HIPs, Tara alone interacts with another cardiac ion channel protein, KvLQT1, in binary yeast two-hybrid assays, but none interacts with Shaker. Each HIP represents a potential target for LQTS to the extent that its expression is required for the normal expression or targeting of HERG channels. The long-range goal of this research is to elucidate the basic biological processes that are disrupted by the disease process. The specific aims of this proposal are: (1) to demonstrate that HERG and the HIPs interact in vivo: (2) to extend our immunocytochemical and electrophysiological analyses, tests for specificity and domain mapping; (3) to determine the necessity of HIP interactions for HERG channels by reciprocal analysis of HERG C terminal truncations and selective disruption of HIPs in native tissues and heterologous systems; and (4) to screen unmapped LQTS families for disease mutations in the genes encoding the HIPs.
34
Potassium
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF K+ CHANNELS IN RENAL COLLECTING DUCT Principal Investigator & Institution: Wang, Wen-Hui; Professor; Pharmacology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 01-JAN-1994; Project End 31-DEC-2003 Summary: The cortical collecting duct (CCD) plays an important role in Na+ reabsorption and K+ excretion. Both K+ secretion and Na+ reabsorption involve several transport proteins including apical Na+ and K+ channels, Na-K-ATPase, and basolateral K+ channels. The basolateral K+ channels participate in generating cell membrane potential and play a critical role in K+ recycling which is important for maintaining the activity of the Na-K-ATPase. Preliminary experiments show that the basolateral small conductance K+ channel (SK) is involved in K+ recycling since the activity of the SK channels is closely related to the apical Na+ transport. That apical Na+ transport acts in concert with Na-K-ATPase and basolateral K+ conductance is important for maintaining a constant intracellular ion concentration and cell volume in the CCD. Therefore, the basolateral K+ channels must be regulated so that K+ recycling can match the apical Na+ transport. We have previously shown that the SK channels are activated by nitric oxide (NO) via a cGMP-dependent pathway. Furthermore, preliminary data demonstrated that inhibiting the apical Na+ transport reduces the activity of the basolateral SK channel activity and the effect of inhibiting Na+ transport depends on NO-cGMP signal transduction pathways. We propose to test the hypothesis that NO is critically involved in coupling the activity of the SK channels to the apical Na+ transport and the activity of Na-K-ATPase. The proposed studies have four Aims. Aim 1 will involve investigating the effects of NO on the SK channels and exploring the mechanisms by which NO regulates the SK channels. Aim 2 will study the role of NO in mediating the Ca2+ effects on the SK channels. Aim 3 will assess the role of NO in mediating the coupling mechanism between apical Na+ transport and basolateral K+ channels and between Na-K-ATPase and basolateral K+ channels. Aim 4 will examine the effect of Angiotensin II on the SK channel and investigate the role of NO in mediating the effect of angiotensin IL. Since the studies are conducted on freshly isolated CCD, the results will provide information essential for understanding the role of NO in the regulation of Na+ and K+ transport in the CCD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: MODULATION OF OLFACTORY BULB NEURON CURRENT PROPERTIES Principal Investigator & Institution: Fadool, Debra A.; Assistant Professor; Biological Science; Florida State University 97 South Woodward Avenue Tallahassee, Fl 323064166 Timing: Fiscal Year 2003; Project Start 01-JAN-1998; Project End 31-DEC-2007 Summary: (provided by applicant): The designed research is a multidisciplinary analysis of the modulation of potassium currents in granule and mitral cells of the olfactory bulb. The broad, long-term objective of this research is to elucidate how neurotrophins and growth factors can utilize ion channels as substrates for phosphorylation to give rise to short-term and long-term plastic changes in synaptic efficacy or to aid in the establishment of neural circuits in the olfactory bulb. Understanding the general principles governing these transduction cascades and the involvement of ion channels will provide information of how protein kinases and protein phosphatases contribute to the onset or severity of specific neuronal diseases,
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35
such as Alzheimer's, or how uncontrolled signaling of these enzymes leads to deregulated cell proliferation and diseases such as cancer and diabetes. Because of the unique trophic and regenerative capacity of neurons in the olfactory system, continual expression of neuromodulators could alter patterns of electrical excitability in addition to their well-studied roles in growth and differentiation. The specific aims of this proposal are to characterize using patch-clamp electrophysiology how receptor-linked tyrosine phosphorylation signaling in the olfactory bulb is altered by sensory experience, patterned electrical stimulation, and trophic factor infusion. By utilizing the cloned, olfactory bulb potassium channel Kv1.3 as a parallel model, combined biochemical measurement of kinase-induced tyrosine phosphorylation, coimmunoprecipitation, and molecular mutagenesis will elucidate the mechanistic details of how ion channels form molecular scaffolds with kinases and adaptor proteins through discrete protein-protein interactions at SH2, SH3, PDZ, and PTB domains. Gene-targeted deletions in Kv1.3 channel, insulin receptor kinase, and TrkB kinase will provide mechanistic details for the role for tyrosine phosphorylation signaling in olfaction and for neuromodulation in the CNS in general, as defined by loss of function experiments (behavioral, biochemical, electrophysiological) using knock-out mice strains. The proposal will provide new important information regarding the integration of signaling molecules by construction of protein-protein interactions with ion channels. Modulation of ion channel function would thus be dependent upon the repertoire of signaling proteins expressed in a given neuron, a background that could change with sensory experience or electrical patterning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR AND PHYSIOLOGIC STUDIES OF A COLONIC K ATPASE Principal Investigator & Institution: Binder, Henry J.; Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUN-1976; Project End 31-MAR-2003 Summary: This application proposes continuation of physiologic and molecular studies of potassium absorption in the rat distal colon. The PI has identified an active K absorptive process in the rat distal colon associated with an apical K/H exchange energized by a novel H,K-ATPase. The PI has also shown that this process is upregulated by both aldosterone and dietary K depletion. The PI's recent studies have focused on correlating the H,K-ATPase activity with the upregulation of K absorption both at the molecular and physiologic levels of study. The PI has reported that H,KATPase of rat distal colon is partially ouabain sensitive, pointing to the possible presence of two different potassium absorptive processes and H,K-ATPase isoforms. His group was recently successful in cloning the HCKalpha1 cDNA. The expression of this cDNA in SF9 cells showed ouabain insensitivity in contrast to studies from other groups using the oocyte expression system. In this proposal he, therefore, plans to determine the physiological function of the transporter cDNAs after transfection in a mammalian cell expression system. Studies are also proposed to determine whether the recently cloned rat colon-specific beta subunit is the elusive and putative beta subunit for optimal functional expression. The PI has identified an ouabain-sensitive Kdependent pHi recovery process in the colonic crypt. The PI hypothesizes that this pHi regulation will be modified by dietary K depletion and will, therefore, represent the second H,K-ATPase function. To identify the second colonic H,K-ATPase, the PI will use a cloning strategy based on its probable upregulation by dietary potassium depletion, its identity to the H-3 domain region rather than to the 5' end of HCKalpha1 cDNA and
36
Potassium
its exclusive localization in colonic crypts. It is also hypothesized that dietary potassium depletion might regulate the second colonic H,K-ATPase (HCKa2 and/or HCKab) at the apical membrane and/or electroneutral KCl cotransport at the basolateral membrane. The PI plans to employ cell and molecular biology studies to accomplish his four specific aims aimed at gaining more understanding of colonic potassium absorption. This proposal certainly has relevance to clinical medicine and would enhance our knowledge of potassium transport. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR VASORELAXATION
BASIS
OF
CAMP
INDUCED
CORONARY
Principal Investigator & Institution: White, Richard E.; Associate Professor; Pharmacology and Toxicology; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the application): Heart failure is often the lethal consequence of a variety of cardiovascular disorders, such as myocardial infarction, hypertension, and coronary artery dysfunction. Although agents that elevate cAMP are commonly used to treat heart failure, knowledge of the cellular/molecular basis of how these drugs act is limited. The long-term goal of the proposed study is to understand how cAMPdependent vasodilators reduce morbidity and mortality of cardiovascular disorders, and thereby suggest new approaches for the treatment of heart failure. Preliminary studies indicate that cAMP-dependent vasodilators relax coronary arteries in vitro by an endothelium-independent mechanism that involves K efflux. Subsequent patch-clamp studies suggest that cAMP opens the large-conductance, calcium- and voltage-activated potassium (BKCa) channel by stimulating the cGMP-dependent protein kinase (PKG) instead of PKA. Preliminary biochemical studies have confirmed this cross-activation. Furthermore, the effects of cAMP can be reversed by agents that inhibit the activity of phosphoprotein phosphatases. Therefore, the hypothesis of the proposed studies is that cAMP-producing agents relax coronary arteries by opening BKCa channels in coronary smooth muscle by stimulating the activity of PKG (but not PKA) and phosphoprotein phoshatase 2A (PP2A). This hypothesis will be tested by employing state-of-the-art techniques of electrophysiology and biochemistry / molecular biology to determine 1) the effect of cAMP-dependent vasodilators on coronary arteries in vitro; 2) the effect of cAMP-stimulating agents on whole-cell and single-channel K currents from single myocytes isolated from coronary arteries; 3) cAMP-dependent 'cross-activation' of PKG; and 4) a potential role of phosphates activity in mediating the response to cAMP in coronary arteries and whether there is a direct interaction between the BKCa channel and PP2A. It is hoped that these studies will lead to the development of novel therapeutic agents that will help reduce the morbidity and mortality associated with heart failure and other cardiovascular diseases (e.g. agents that target BKCa channels of phosphoprotein phosphatases). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF K+ CURRENT DURING SECRETION Principal Investigator & Institution: Nehrke, Keith W.; Assistant Research Professor; Oral Biology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2003
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Summary: Salivary gland hypofunction enhances the risk of oral and systemic disease, and results in a deterioration in the ability to chew, swallow, and speak. The secretion of saliva helps to maintain oral health by lubricating and hydrating mucosal surfaces, as well as protecting the oral cavity from mechanical and chemical stresses and microbial invasion. The process of secretion couples the action of multiple ion channels, cotransporters, and exchangers to drive the transepithelial movement of water. In particular, a calcium-activated potassium channel located on the basolateral membrane of acinar cells is coupled to a calcium-activated chloride channel on the apical membrane, and these channels work together to allow stimulated secretion by muscarinic agonists. The molecular identity of each of these channels remains unknown. Until recently, the large-conductance BK (slo) channel was thought to carry the majority of the calcium-activated potassium current during stimulated secretion. However, pharmacological evidence exists that secretion in the submandibular gland occurs primarily through the action of an intermediate-conductance calcium-activated potassium channel. A candidate cDNA, termed SK4/IK1, was recently cloned based upon homology with the SK family of small-conductance calcium-activated potassium channels. Over the range of tissues examined, the highest level of expression of the human IK isoform, hIK1, occurs in salivary glands. To better define the involvement of IK1 in stimulated secretion, we propose to use molecular and immunological tools to localize the IK1 transcript and protein in the parotid gland of a mouse model system. We will further exploit the utility of this system by studying the physiological consequences of the loss of mIK1 activity. Using a transgenic strain containing a targeted gene disruption of mIK1 which we are generating presently, we will examine mIK1-mediated changes in saliva flow rate and ion composition. Because recombinant mIK1 has been suggested to convey a novel ability to undergo regulatory volume decrease (RVD) in Xenopus oocytes, we will further assay whether mIK1 is involved in RVD in a mammalian expression system and in the parotid gland. Finally, we will look at compensatory changes that occur in the expression of functionally-related ion transport proteins in the transgenic strain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR PHARMACOLOGY OF AN INHERITED HEART DISEASE Principal Investigator & Institution: Kass, Robert S.; Professor of Pharmaclogy and Chairman; Pharmacology; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2001 Summary: (adapted from the applicant's abstract): The overall goal of the research proposed in this application is to develop novel therapeutic approaches, based on specific properties of an inherited molecular genetic defect, to the management of electrophysiological aberrations that occur in two forms (LQT-3 and LQT-1) of an inherited cardiac disorder, the long QT syndrome. This project is designed to integrate clinical, molecular, and cellular studies in order to test the overall hypothesis that mutations in genes that encode the heart sodium channel alpha-subunit (SCN5A), and the slow potassium channel current (IKs) KvLQT-1/or minK cause identifiable changes in expressed sodium and potassium channel activity that underlie diseased-associated changes in repolarization and associated rhythm disturbances and that, in turn, make mutant channels distinct targets of therapeutic drugs. Thus, it is the long-term goal of this research to develop a more effective and specific therapeutic approach to manage and prevent life-threatening arrhythmias associated with this disease and that therapies will be developed that are targeted for specific gene defects. In vitro experiments will be
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Potassium
carried out using patch-clamp procedures to measure whole-cell currents expressed in human embryonic kidney cells (HEK293) and Chinese hamster ovary (CHO) cells that have been transiently transfected with cDNAs encoding wild-type (hH1) and LQT-3 mutant (deltaKPQ) forms of the human sodium channel alpha-subunit as well as cells that have been co-transfected with cDNA encoding wild-type and mutant forms of KvLQT1 and minK. Experiments focusing on possible roles of adrenergic modulation, cellular pH and calcium influx will test for voltage-dependent kinetic and neurohumoral factors that may distinguish KvLQT-1 from SCN5A-derived phenotypes. In addition, experiments will be carried out on each gene defect testing for specific pharmacological interventions that are designed to modulate expressed channel activity in a manner to compensate for individual gene defects. The principal investigator will consult with Dr. Arthur J. Moss at the University of Rochester, who will be directing parallel clinical studies in order to optimize pharmacological approaches to manage and correct identified gene defects. Experimental data obtained from recombinant channel activity will be shared and integrated with the results of clinical non-invasive electrocardiologic studies that will be carried out in vivo on carriers vs. non-carriers of the LQT-1 and LQT-3 gene mutations to optimize experimental design and therapeutic approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR COTRANSPORTERS
PHYSIOLOY
OF
BRAIN
CATION-CL
Principal Investigator & Institution: Delpire, Eric J.; Anesthesiology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 30-JUL-1999; Project End 31-AUG-2007 Summary: (provided by applicant): g-Aminobutyric Acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain, and plays a prominent inhibitory role in the brainstem and spinal cord as well. One mechanism through which GABA produces its inhibitory action is via GABAA receptors which produce fast synaptic inhibition of neurons by activation of intrinsic CI- channels. GABA opening of CIchannels produces an inward movement of CI-, driven by a low intracellular CIconcentration which is maintained by an active CI- extrusion mechanism: presumed to be the neuronal-specific isoform of the K-CI cotransporter, KCC2. We have disrupted Sic12a5, the gene encoding this isoform of the K-CI cotransporter, and the homozygous mutant mice die shortly after birth of repeated seizures. Epileptic seizure activity in the KCC2 knockout brain suggests hyper-excitability, in agreement with the putative role of KCC2 in controlling hyperpolarizing GABA responses. This proposal is aimed at understanding the role of KCC2 in controlling CNS excitability and epilepsy. We will 1) investigate the developmental role of KCC2 in regulating intracellular CI- and controlling the maturation of GABA hyperpolarization, 2) investigate the role of KCC2 in preventing hyper-excitability and the participation of the cotransporter in depolarizing GABA responses during high frequency synaptic activation. This will be achieved through detailed electrophysiological measurements in hippocampal slices and isolated cortical neurons, 3) develop brain-region-specific and inducible knockout of KCC2 to study the knockout phenotype in the adult and examine the effect of graded reduction in KCC2 expression, and 4) examine the determinants of KCC2 function and regulation, by focusing mainly on phosphorylation/dephosphorylation of the protein. The epileptic seizure phenotype of the KCC2 knockout mouse demonstrates the importance of KCC2 in preventing hyper-excitability and controlling CNS function. Results of these molecular, physiological, and behavioral studies will lead to a better
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understanding of the relationship between cation-chloride cotransporters, ion homeostasis, synaptic transmission and brain excitability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUSCARINIC TRANSDUCTION
AND
ADENOSINE
RECEPTOR
SIGNAL
Principal Investigator & Institution: Mortensen, Richard M.; Assistant Professor of Physiology & Inte; Physiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from the Investigator's Abstract) In cardiac tissue acetylcholine liberated from parasympathetic nerves acts via the m2 receptor to slow the heart (negative chronotropy) and decrease the force of contraction (negative inotropy). Adenosine, produced locally in the heart in response to ischemia, acts through A1 receptors to produce similar effects. These receptors can activate a number of different pertussis toxin sensitive G-proteins to directly and indirectly (via second messengers) regulate ion channels (inwardly rectifying potassium channels, acetylcholine activated potassium channels, L-type calcium channels, and pacemaker channels). Although some specificity in the signal transduction cascade has been defined, the exact role of these subtypes is unclear. The G-proteins in these pathways have been reported to be upregulated in heart failure and pertussis toxin sensitive pathways play a role in decreased adrenergic responsiveness. In order to correlate physiological function and the function of the pathways activated, targeted disruption of alpha subunit genes (alpha-i2, alphai3, alpha-o) in mice and in embryonic stems cell has been performed. Inactivation of each alpha subunit has a specific disruption of some signaling pathways but not others. Alpha-o inactivation affects L-type Ca current and negative chronotropy whereas alphai1 and alpha-i3 disrupt activation of the acetylcholine activated potassium channel. This application proposes to define the specific role of these intracellular signaling cascades in the heart. The ionic channel, chronotropic and inotropic responses ro A1 adenosine and carbachol stimulation will be further defined in knockout mice and knockout cell lines. The mechanisms for these effects will be explored by characterizing receptor number and affinity, expression of other G proteins, and activation of second messenger cAMP. The structural basis for G-protein specificity in effector coupling will be studied by the production of mutant alpha-o molecules and testing their ability to restore functional coupling of effectors to receptors. These experiments should provide important information on the specificity of signal transduction by G proteins in heart. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEOCORTICAL EPILEPSY DURING DEVELOPMENT Principal Investigator & Institution: Hablitz, John J.; Professor; Neurobiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-1986; Project End 31-MAR-2006 Summary: Neuronal migration disorders resulting in cortical dysplasia, microgyria, and hectrotopias are associated with intractable seizure disorders in humans. We have used the rat freeze lesion model to examine neural mechanisms underlying hyperexcitability in dysplastic cortex. Proposed studies will combine optical imaging and whole-cell voltage-clamp techniques to test specific hypotheses about mechanisms that control excitability in the dysplastic cortex. These mechanisms are alterations in N-methyl-Daspartate receptors (NMDARs) in local horizontal pathways and remodeling of
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GABAergic networks. Experiments will investigate if the enhanced spread of voltage sensitive dye signals we observed in slices from dysplastic cortex is due to an increased contribution from NMDARs in intracortical horizontal pathways. It will be determined if blockage of NMDAR activation changes the spatial and temporal extent of cortical circuit activation. We will examine if NR2B subunit containing NMDARs in lesioned cortex confer hyperexcitability through the prolongation of excitatory postsynaptic currents. It is hypothesized that NMDAR EPSCs are prolonged in dysplastic cortex and resemble those seen at earlier stages of development in normal neocortex. Anatomical studies will determine if there are changes in the number or extent of axon collaterals forming horizontal connections. We will also determine the site of origin and pattern of spread of depolarizing GABA waves in dysplastic neocortex. It is hypothesized that reorganization of GABA-ergic networks in dysplastic cortex will result in different patterns and rates of propagation. We will delineate the site of origin and pattern of spread of depolarizing GABA waves in dysplastic neocortex. It is hypothesized that a propagating wave of potassium results in spreading changes in intracellular chloride due to activity of potassium-coupled chloride cotransporters. Changes in extracellular potassium and application of transport blockers are predicted to change or block propagation. Glial cells are coupled by gap junctions and participate in spatial buffering of potassium. Disruption of gap junctions is predicted to change or block propagation. These studies will provide important new information about NMDA and GABA receptors in neocortex. They will also contribute to our understanding of the functional changes at both the cellular and circuit level, responsible for the intrinsic hyperexcitability of dysplastic cortex in the freeze lesion model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROGENETICS OF THE SEIZURE (DERG) POTASSIUM CHANNEL Principal Investigator & Institution: Massa, Enrique; Associate Professor; Texas A&M University-Kingsville 700 University Blvd Kingsville, Tx 78363 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: Potassium channels make up a diverse group of ion channels that play integral in roles action potential generation and fine-tuning of firing properties of excitable cells. The ether-a-go-gorelated (ERG) potassium channels are a relatively new family of potassium channels. The human ERG ismutant in a form of familial Long QT syndrome or sudden cardiac death. The role of ERG in cells is not fully understood and the identification of mutations in this channel warrant the further examination of the function of this ion channel. The previous funding period for this proposal resulted in the characterization of the Drosophila ERG channel which is mutant in the seizure mutation. The seizure (DERG) channel transcriptional start sites were identified and mapped to three distinct promoters which exhibit cell-specific transcriptional regulation patterns. This proposalexamines the promoters of DERG and their control by specific DNA elements. We propose to examine the seizure (DERG) channel gone by transgenic regulation of promotedreporter gone fusions and identificationof conserved regulatory elements acrossthree Drosophilid species. The coordinate transcriptional regulation of seizure (DERG) and gamma-SNAPwill also be examined. The gamma-SNAP gene lies on the opposite DNA strand and transcribes antiparallel to DERG. The most proximal seizure (DERG) promoter overlaps with the promoter of gamma-SNAP. Interestingly, both genes exhibit the same expression profile on Northern blot analysis. We propose to examine this coordinate regulation by identifying the minimal gamma-SNAP promoter and correlating with the minimal regulatory sequences of the proximal seizure (DERG)
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promoter. We will also utilize genetic screens to identify genes that modify seizure mutantphenotypes and compdse either accessory subunitsor play similar roles in modulating membrane excitability. In addition, electrophysiological analysisand recombination mapping of the identified mutants will be performed on previously identified seizure (DERG) modifiers. The ease of generating mutations in Drosophila and the availability of the annotated genome allows us to combine physiological analyses with genetics approaches to address questions pertaining ion channel regulation and function. These studies may shed light upon the physiological role of ERG and provide evidence of the pathophysiology of LQT syndrome and epilepsy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NICOTINE INDUCED CEREBROVASCULAR DYSFUNCTION Principal Investigator & Institution: Mayhan, William G.; Professor, Vice Chair of Physiology; Physiology and Biophysics; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant) While cigarette smoke contains many toxic substances, it appears that nicotine may be responsible for the adverse effects of tobacco products on the cardiovascular system. Recent studies suggest that nicotine impairs nitric oxide synthase-dependent, but not -independent, dilatation of peripheral arterioles. While there is evidence, which suggests that smoking is a risk factor for the pathogenesis of cerebrovascular disorders, including stroke, mechanisms, which contribute to the development of cerebrovascular disorders remain uncertain. Thus, the central hypothesis of this application is that nicotine contributes to the pathogenesis of cerebrovascular abnormalities via alterations in cellularprocesses, which govern reactivity of cerebral arterioles. We propose two specific aims. In aim #1, we will determine the effects of nicotine on nitric oxide synthase-dependent and -independent responses of cerebral resistance arterioles. In addition, we propose to examine several potential mechanisms by which acute and chronic exposure to nicotine might influence nitric oxide synthase-dependent reactivity of cerebral arterioles. Our hypothesis is that nicotine impairs dilatation of cerebral arterioles via impairment in the arginine/nitric oxide syntheses biosynthetic pathway, and/or stimulation of oxygen derived free radicals. In aim #2, we will determine the effects of nicotine on reactivity of cerebral arterioles to activation of potassium channels. Activation of potassium channels plays an important role in the regulation of cerebrovascular tone in response to a variety of stimuli. We propose to examine the effects of nicotine on reactivity of cerebral arterioles to activation of potassium channels and examine potential mechanisms, which contribute to altered responses of cerebral arterioles during activation of potassium channels. Our hypothesis is that nicotine alters dilatation of cerebral arterioles in response to activation of potassium channels. In summary, studies proposed in this application will be the first comprehensive attempt to examine the effects of nicotine on cellular pathways, which govern reactivity of cerebral arterioles. Our studies will provide valuable insights into mechanisms by which nicotine may contribute to cerebral microvascular dysfunction, including stroke, observed in cigarette smokers and users of tobacco products. In addition, results of these studies may provide insights regarding possible therapeutic approaches for the treatment of nicotine-induced vascular dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOPHYSIOLOGY OF CHRONIC CEREBRAL VASOSPASM Principal Investigator & Institution: Macdonald, R. Loch.; Associate Professor; Surgery; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 31-MAY-2006 Summary: (provided by applicant): We are investigating cerebral vasospasm which is an important cause of cerebral ischemia after subarachnoid hemorrhage (SAH). The longterm objective of this grant is to determine the mechanism of vasospasm after SAH and to thereby develop treatments that will prevent and/or reverse it. We have shown that hemoglobin causes vasospasm and that vasospasm is associated with impaired arterial relaxation. One mechanism of hemoglobin-induced vasospasm may be the binding and removal of nitric oxide (NO). We have used electron paramagnetic resonance (EPR) spectroscopy to detect nitrosyl hemoglobin in the subarachnoid space after SAH, proving that this mechanism occurs. We will therefore test the hypothesis that there is an NO-reversible component of vasospasm by: 1) defining the extent to which vasospasm is reversible with NO donors in a monkey model of SAH; 2) measuring heme-NO adducts (nitrosyl hemoglobin) by EPR spectroscopy in clots removed from the subarachnoid space of monkeys at different times after SAH; 3) quantifying NO in the perivascular space at different times after SAH in monkeys; and 4) defining the time course of changes in and the immunohistochemical locations of the 3 isoforms of NOS in cerebral arteries and perivascular blood clot after SAH in monkeys. Second, because vasospasm does not seem to be completely preventable by NO donors, we will investigate mechanisms of NO-independent vasospasm by: 1) measuring protein kinase G messenger ribonucleic acid, protein and activity during the time course of vasospasm in monkeys; and 2) assessing calcium sensitivity of monkey cerebral arteries during the time course of vasospasm. In a rat model, we will assess the contribution of other downstream effectors of NO-induced relaxation by: 1) assessing potassium channel function during vasospasm (calcium-activated potassium channel density, single channel conductance, and open probability will be assessed using whole cell and single channel patch clamp recordings of isolated vasospastic rat cerebrovascular smooth muscle cells); and 2) measuring whole cell calcium currents during vasospasm in rats because assessment of potassium channel function requires knowledge of intracellular calcium and because smooth muscle calcium homeostasis may be altered during vasospasm after SAH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PDZ INTERACTION AND INWARD RECTIFIER K+ CHANNEL FUNCTION Principal Investigator & Institution: Vandenberg, Carol A.; Associate Professor; None; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): The strong inward rectifier potassium channels are involved in action potential repolarization, modulation of cell excitability, and determination of cell resting potential in the brain and other excitable cells. Indeed, mutations in these channels are associated with defects in cell excitability, periodic paralysis, cardiac arrhythmias, and developmental abnormalities. Recently, it has been demonstrated that proteins that are associated with ion channels may modulate the functional properties of the channels, and such interactions may have profound implications in normal physiology and disease. Defects in channel-interacting proteins could lead to problems in channel expression, membrane targeting, association of
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channels with signaling complexes, and channel electrical activity. This proposal aims to identify and characterize the proteins that interact with inward rectifier potassium channels. Recently, we have identified such an interaction between inward rectifier channels and the scaffolding protein SAP97 in the brain. The goal of this project is to identify the complex of proteins that associate with inward rectifier potassium channels and to analyze the functional ability of these proteins to cluster, localize and regulate the activity of the channels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHOSPHOINOSITIDES AND ATP-SENSITIVE K+ CHANNELS IN HEART Principal Investigator & Institution: Fan, Zheng; Assistant Professor; Physiology and Biophysics; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2003; Project Start 01-SEP-1997; Project End 31-MAR-2007 Summary: (provided by applicant): ATP-sensitive potassium channels (KATP channels) are present in many cell types, and their activity in cardiac myocytes is thought to be related to the etiology of ischemic heart disease. KATP channels sense changes in intracellular ATP concentrations and convert this signal to changes in membrane potential and membrane potassium permeability. Previous studies in this and other laboratories have shown that membrane phosphoinositides (PPIs) modulate KATPchannel activity and ATP sensitivity. Electrophysiological results suggest that these effects are due to a direct and specific interaction between PPIs and the channelforming subunit (Kir6.2) of the KATPchannel. The overall objective of this research proposal is to clarify the structural basis responsible for this specific PPI-KATP channel interaction, and to elucidate how it affects ATP sensitivity. Our recent work using biochemical binding assays shows that the ability of PPIs to bind Kir6.2 depends on the headgroup of the PPI. We have also shown that PPIs reduce photolabeling of Kir6.2 by ATP photoaffinity analogs. Based on these preliminary results, we propose to address the following Specific Aims: (1) We will investigate the selectivity of PPI binding and structural requirement in the PPI-KATP channel interaction in order to determine whether PPIs act on Kir6.2 through a direct and structure-specific interaction. (2) We will investigate the structural mechanism for ATP binding and whether PPIKir6.2 association modulates ATP binding. (3) We will investigate the role of SUR2, the regulatory subunit of the KATPchannel, in PPI-KATP channel interaction and PPI modulation of ATP binding. Using a variety of complementary techniques, including binding assays, photolabeling, enzymatic digestion analysis, sitedirected mutagenesis, and electrophysiological measurements, we will provide direct evidence demonstrating how PPIs and KATP channels interact, and how this interaction modulates ATP binding. The results of this work will significantly improve our understanding of how KATpchannels respond to PPI-mediated signal transduction in heart. The results will also offer insightful structural information on the ATP sensitivity of this channel. In the broader area of ion channel physiology, knowledge gained from study of the mechanisms of PPI-KATP channel interaction and use of KATPchannel function as a model system will help us to understand the general principles that dominate specific lipid-channel interactions and channel functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POLARIZED TRAFFICKING OF K+ CHANNELS IN THE KIDNEY Principal Investigator & Institution: Welling, Paul A.; Associate Professor; Physiology; University of Maryland Balt Prof School Baltimore, Md 21201
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Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Polarized trafficking, appropriate surface expression and disparate regulation of at least two different potassium channels on opposite membrane domains of the renal cortical collecting duct (CCD) principal cell insure an efficient potassium secretion process and potassium homeostasis. Here, we propose to elucidate the molecular mechanisms governing polarized targeting and surface expression of the basolateral CCD channel, Kir 2.3. Our previous work suggests a hierarchical trafficking program, involving a novel biosynthetic sorting process and dynamic, PDZ dependent retention at the basolateral membrane. To critically test this hypothesis, a stepwise multidisciplinary approach, combining molecular genetics, cellular biology, electrophysiology and transgenics, will be employed to answer the following questions: 1. How is the basolateral trafficking signal in Kit 2.3 interpreted within the biosynthetic sorting pathway? This aim is designed to critically test the role of novel biosynthetic sorting machinery candidates. 2. Does internalization of Kit 2.3 occur via clathrin-dependent mechanism, involving a direct interaction with the ? subunit of AP2 adaptor complex. This aim is designed to elucidate the molecular mechanisms involved in endocytotic trafficking of Kit 2.3, providing a context to understand how PDZ interactions regulate Kit 2.3 expression. 3. Does interaction with the Lin-7/CASK PDZ complex coordinate basolateral expression of Kit 2.3 by limiting endosomal trafficking. In this aim, plasma membrane turnover rate and intracellular trafficking of externally tagged channels will be assessed in the absence and presence of dominant interfering Lin-7 constructs. 4. How is interaction with MOPP, a unique PDZ protein, regulated to control surface expression of Kir 2.3? This aim is designed to test the hypothesis that MOPP acts as a natural negative regulator of Lin 7 PDZ scaffoldingcomplexes. 5. Does Lin-7 interaction regulate Kir 2.3 expression in the CCD during potassium adaptation? In this aim, we will determine if Lin -7 interaction underpins the physiological regulation of Kir 2.3. Wild-type and Lin-7 knockout mice will be studied. These studies represent a timely and important extension of the principal investigator's work, and should ultimately provide considerable insight into the basis of renal K handling and K homeostasis in health and disease while illuminating new and presently unexplored mechanisms controlling membrane-protein sorting in the kidney. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POTASSIUM AND THE MUSCLE REFLEX IN HUMAN SUBJECTS Principal Investigator & Institution: Daley, Joseph C.; Medicine; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: PROPOSAL (Adapted from the applicant's abstract): The long-term goal of the principal investigator (PI) is to become a clinician scientist examining issues pertaining to autonomic regulation in health and disease. The main objective of this project is to examine the metabolic and mechanical factors that initiate and sustain the muscle exercise pressor reflex. This reflex is a major determinant of blood flow and pressure during exercise. In addition, diseases, such as congestive heart failure (CHF) are associated with pathologic activation of this reflex and may contribute to the morbidity and mortality of this common disorder. Two basic theoretical components of neural control of circulation predominate. "Central command," a feed forward signal emanating from the central motor areas, suggests that neural motor and sympathetic activation occur in parallel. This system may be integrally linked to skeletal muscle metabolic demand. The second component of the reflex is the muscle reflex, and is the subject of this investigation. It is clear chemical byproducts of muscle contraction can
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evoke a pressor response. However, the specific interstitial chemical(s) that stimulate the muscle fiber afferents, and engage the reflex, remains an area of considerable controversy. This study proposes investigation of the relationship between interstitial potassium concentration and muscle sympathetic nervous activity (MSNA). Recent studies have implicated potassium as a potential mediator of the muscle reflex; however, conclusive evidence linking interstitial K+ with MSNA does not exist. The investigators will examine the "real time" interstitial concentration of potassium in exercising muscle and MSNA simultaneously, as well as venous plasma effluent, to further our understanding of this relationship. In addition, they propose examination of the exercise pressor response after directly inhibiting Na+/K+ pump with regional digoxin administration. This project will further increase their knowledge of the mechanisms regulating the muscle exercise pressor response, and may add to understanding of the role of this reflex in diseases such as CHF. The PI has been funded by an NRSA (F32 HL10320). This proposal will give the PI the additional support and training necessary to become an independent investigator. The mentor for this project has recently received a K24 Award and is the Program Director (PD) of their General Clinical Research Center (GCRC). Accordingly, he is ideally suited to serve in this capacity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POTASSIUM CHANNEL GATING Principal Investigator & Institution: Mackinnon, Roderick; Associate Professor; Lab/Mol Neurobiology/Biophysic; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2003; Project Start 01-APR-1990; Project End 31-JUL-2007 Summary: (provided by applicant): The long-term objective of this project is to understand the mechanisms of K + channel gating, that is, how the opening of K + channels is regulated in living cells. Potassium channels play a central role in many different cellular processes including the production of electrical impulses in the nervous system, the control of heart rate, blood pressure, and the secretion of hormones such as insulin. For these reasons, a deeper understanding of how K+ channels open and close - based on their chemistry and structure -will eventually enhance our ability to treat many illnesses that afflict humans, including seizure disorders, cardiac arrhythmias, hypertension, and asthma. A wide range of techniques will be applied to the study of K + channel gating, including molecular biology, protein biochemistry, electrophysiology, and X-ray crystallography. Three fundamentally different gating mechanisms will be studied: channel opening induced by Ca 2+ binding, by G-protein binding, and by membrane voltage. The first of these mechanisms underlies muscle contraction and signal processing in the nervous system, the second mechanism controls heart rate and neurotransmitter responses, and the third is responsible for generating electrical impulses known as action potentials in both nervous and non-nervous cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POTASSIUM HOMEOSTASTASIS OF KV 1.3-DEFICIENT MICE Principal Investigator & Institution: Xu, Jianchao; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 31-JAN-2006 Summary: (adapted from the application) Disturbances of potassium homeostasis can result in fatal consequences such as cardiac arrest. The kidney is a vital organ that maintains serum potassium concentration in a very narrow range. To achieve this, renal
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epithelial cells are equipped with membrane transporters such as Na-ATPase and K channels. The exact mechanism of K absorption and secretion in the kidney is not completely understood, however, recent progress suggests that potassium channels may play an important role in the process. In addition to inward rectifier K channels, voltage-gated K channels are also expressed in kidney. Dr. Gary Desir's laboratory has identified several such channels. Two of these have been extensively characterized: Kv1.3 and KCNA10. Although the precise physiological role of these channels in renal K homeostasis is unclear, it is postulated that Kv1.3, in conjunction with ATP-sensitive KATP channels, mediates K exit into interstitium where K can be returned to blood stream or accumulated and recycled back into the cell by Na+,K+-ATPase pump. KCNA10 may participate in K transport, the regulation of vascular tone, the cardiac action potential, and cortisol secretion. To test these hypotheses, I will examine the subcellular localization of Kv1.3 in the renal epithelia, and study the Kv1.3 function in vivo using gene-targeting. The Specific Aims of the project are: (1) Localization of Kv1.3 in renal epithelial cells. (2) Generation of Kv1.3-deficient mice. (3) Characterization of the K0.3-deficient mice. (4) Generation of KCNA10 knockout mouse and Kv1.3/KCNA10 double knockout mouse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RACE AND CONTROL OF TISSUE RENIN ANGIOTENSIN SYSTEMS Principal Investigator & Institution: Fisher, Naomi D.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-FEB-1996; Project End 31-JAN-2006 Summary: (Adapted from the applicant's abstract) Hypertension is more prevalent in blacks than in Caucasians and is disproportionately severe, leading to a higher rate of clinical complications. The overall hypothesis is that the increased tissue AngII activity in blacks, usually attributed to "race" itself, is actually determined by identifiable genetic factors. Candidate genes within the RAAS include angiotensinogen, the AT1 receptor, aldosterone syntheses, 11-OH-steroid dehyodrogenase and angiotensin-converting enzyme. The phenotypes of increased AngII activity may be compounded by decreased activity of vasodilator pathways (preliminary data highlight racial differences in the kallikreinkinin system), adding kallilrein and endothelial nitric oxide syntheses (eNOS) to the list of candidate genes. They plan to use physiologic and pharmacologic tools to support this hypothesis, devoting special recruitment methods to enroll large numbers of black subjects. Especially among blacks, the interacting contribution of environmental factors to the development and maintenance of hypertension cannot be ignored. We plan to explore three factors that may interact with genetic predisposition to hypertension. The first is obesity, already shown to predict abnormal renal responses to AngII, with its effect dependent upon angiotensinogen genotype. The most likely elemental candidate interacting with genotype is dietary potassium; urinary potassium has often measured lower among blacks, and potassium is likewise intimately involved in control of the tissue kallikrein-kinin system. Finally, our preliminary evidence suggests that a salient feature describing blunted AngII adrenal responsiveness among Caucasians - a sexual dimorphism - is absent among blacks. Young black women in particular lack the protection seen in young white women, which may underlie the higher cardiovascular morality rates seen in black women. They hypothesize that genetic differences in blacks modulate estrogen's effect on the RAAS, perhaps by interfering with its binding to estrogen response elements and therefore gene transcription. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF COLONIC H-K-ATPASE IN THE KIDNEY Principal Investigator & Institution: Soleimani, Manoocher; Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 08-JUN-1998; Project End 31-MAY-2002 Summary: (Adapted from the Applicant's Abstract): Both the gastric (g) and colonic (c) isoforms of H+/K+-ATPase (HKA) are expressed at low levels in renal collecting duct (CD) cells but the functional role(s) for these HKA remain uncertain. They propose that cHKA specifically plays a pivotal role in renal HCO3-, K+ and Na+ transport in several pathophysiologic states. Our studies show that cHKA mRNA and or activity is increased in conditions associated with increased HCO3- delivery to the CD (proximal RTA) or in potassium depletion (KD). Interestingly, hypophysectomy (HPX) suppresses increased expression of cHKA in KD but not in proximal RTA. They hypothesize that cHKA is vital to acid-base, K+ and Na+ homeostasis: Upregulation of cHKA blunts HCO3- loss in instances of increased delivery of HCO3- to the distal nephron and accelerates K+ and Na+ reabsorption in KD. To elucidate this hypothesis, we propose to examine the molecular and functional regulation of cHKA in: a) three models associated with increased delivery of HCO3- to the distal tubule but different states of acid-base balance: acetazolamide (acidosis), chloride depletion (alkalosis), and NaHCO3 loading (normal); and b) in potassium depletion. Acid-base and electrolyte changes, HCO3reabsorption in isolated perfused CCD and OMCD, and cortical, medullary, and nephron-segment mRNA and protein for cHKA will be determined in rats and mice (both cHKA-deficient transgenic and wild-type) with KD or increased HCO3-delivery to distal tubules. In KD rats experiments will be repeated in HPX + hormonal replacement. Lastly, they will examine transcriptional regulation of cHKA. Mice transgenic for a cHKA promoter-luciferase reporter (PLR) construct will be studied in the above models. Coupled with the data from (a) and (b) above, these studies suggest possible signals for study in cultured renal cells. These will be transiently transfected with deleting constructs of LR and studied under in vitro conditions to determine the sensing elements within the promoter of cHKA cDNA. Insight into regulation of cHKA will significantly enhance our knowledge on a variety of pathologic conditions associated with electrolyte and acid-base abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF ION CHANNELS BY METHIONINE OXIDATION Principal Investigator & Institution: Hoshi, Toshinori; Physiology and Biophysics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 31-JAN-2002 Summary: Previous studies have shown that, like many other proteins, amino acid residues of potassium channels are subject to oxidation by reactive oxyge species. Oxidation of amino acid residues, especially of cysteine residues, is well documented. Methionine can be readily oxidized to form methionine sulfoxide. Oxidation of methionine is unique in that it is reversible and that reduction of oxidized methionine requires an enzyme, methionine sulfoxide reductase (MsrA). The reversibility of methionine oxidation catalyzed by MsrA suggests that it could act as an important cellular regulatory mechanism. Preliminary results indeed suggest that oxidation of methionine residues in Shaker potassium channels has dramatic effects on the channel activation and deactivation. This project will establish the dynamic functional role of methionine oxidation as a key player in regulation of cellular excitability. Shaker potassium channels will be expressed in Xenopus oocytes and their macroscopic and
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single-channel current properties examined using the two-electrode voltage clamp and patch-clamp methods. The effects of methionine mutations and MsrA co-expression will be quantitatively assayed to elucidate the biophysical mechanisms involved. The importance of methionine oxidation an its reversal by MsrA in a variety of other potassium channels and voltage-dependent calcium channels will also be examined. Results from the proposed research will establish a novel cellular excitability mechanism involving methionine oxidation and reduction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF KIR CHANNELS IN RETINAL GLIAL CELLS Principal Investigator & Institution: Eaton, Misty J.; Assistant Professor; Universidad Central Del Caribe Bayamon, Pr 009606032 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-DEC-2005 Summary: Potassium inwardly rectifying channels (Kir) stabilize the membrane potential and carry K+ ions. Kir are dominant in the astrocytic Muller (glial) cells responsible for maintaining extracellular homeostasis in the retina. Excitation of neurons increases levels of extracellular potassium ions (K+) at synapses, which if uncorrected would result in depolarization of neurons and a loss of synaptic transmission. Kir channels serve to equaliz4e intraretinal K+ gradients by a mechanism called spatial buffering or K" siphoning. Glial cells carry K+ currents inward in regions where the extracellular K+ concentration is increased and outward at more distant regions. In order to extrude K+ in distant regions, Muller cells need either one type of Kir with rectification that can be quickly regulated (to have outward current) or to have express additional Kir channels with weak or little rectification. The only Kir described in Muller cells to date is Kir 4.1. This channel is strongly rectifying and requires ATP to function and, thereby, could not function for K+ siphoning or when ATP is depleted (i.e., anoxia.). Our preliminary data demonstrate the existence of another Kir subunit, Kir 6.1 (KATP) expressed in Muller cells, which may complete the above- mentioned requirements. Our working hypothesis is that there are two possible ways of how these different subunits (Kir4.1 AND Kir6.1) may collaborate in Muller cell functioning, (i) by co-expression in functional heteromers, or (ii) by mutual switching between two distinct homomeric channels. Our long-term goal is to determine the identify and regulation of Kir channels from retinal glial cells. This will be accomplished using a multi-faceted approach. (1) By determining which Kir subunits are expressed in retinal Muller (glial) cells using immunocytochemistry. (2) By determining the electrophysiological properties and regulation by ATP, spermine and pH of homomeric and heteromeric channels expressed in HEK cells. (3) The electrophysiological properties and regulation of Kir channels and dissociated Muller cells will be compared with the expressed channels and will be examined under different metabolic conditions. The results of these studies will provide insight into normal Kir channel function as well as Kir channel regulation during anoxia and hypoglycemia. when ATP is depleted. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF PULMONARY VASCULAR TONE DURING CIRRHOSIS Principal Investigator & Institution: Carter, Ethan P.; Associate Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005
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Summary: The cellular mechanisms governing the regulation of pulmonary vascular tone are complex and incompletely understood, particularly during pathphysiological conditions. One such pathophysiological condition is hepatopulmonary syndrome. Hepatopulmonary syndrome is a clinical triad of advanced liver disease (usually cirrhosis), pulmonary gas exchange abnormalities (i.e. shunting) leading to severe systemic arterial hypoxemia, and widespread pulmonary vasodilations in the absence of intrinsic cardiopulmonary disease. This syndrome occurs in 15 - 30 percent of cirrhotic individuals and vastly complicates their treatment. Nitric oxide (NO) has been postulated to be central to the development of hepatopulmonary syndrome. An animal model of hepatopulmonary syndrome recently has been developed in rats that has proven useful for investigating to pathogenesis of hepatopulmonary syndrome. These animals have intrapulmonary shunting and hypoxemia. The mechanisms linking NO to the development of hepatopulmonary syndrome have not been defined. This proposal investigates the underlying mechanisms of hepatopulmonary syndrome using a comprehensive approach of in vivo and in vitro experimental strategies. We provide preliminary data demonstrating that in addition to elevated NO and eNOS, expression in lung of the vasocontrictor endothelin (ET-1) is decreased in cirrhotic rats. Evidence is also provided showing that vascular smooth muscle potassium channels are activated during cirrhosis. These are the first data ever, providing a mechanism for the pulmonary vasodilation and blunted hypoxic pressor response during cirrhosis. Additional data is shown demonstrating that during cirrhosis the stress response gene heme oxygenase-1 (HO-1) is significantly upregulated in lung and liver and decreased in kidney. HO-1 enzymatic activity liberates CO, a known vasodilator that can act via cGMP-dependent and -independent pathways. Therefore, it is possible that the tissue-specific regulation of the HO-1/CO axis contributes to the pulmonary vasodilation and renal vasoconstriction during cirrhosis. Finally, to investigate the role of NO in alterations to ET-1, potassium channels, and HO-1, cirrhotic rats were chronically treated with a NO inhibitor. This treatment resulted in a complete reversal of the cirrhotic associated changes to gene expression. Taken together, our data suggest that during cirrhosis, NO is central to the development of hepatopulmonary syndrome acting not only as a vasodilator but also as a regulator of gene expression of ET-1, potassium channels, and HO-1. We will test the hypotheses that: (1) chronic NO elevation during cirrhosis renders the pulmonary circulation unresponsive to hypoxia via direct vasodilatory actions and indirect modifications to gene expression; (2) factors released by the cirrhotic liver regulate pulmonary vascular tone; (3) HO-1 derived CO contributes to the pulmonary vasodilation during cirrhosis. This project will not only define the cellular basis for hepatopulmonary syndrome, but will also contribute to our understanding of how pulmonary vascular tone is controlled at the most basic level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF UTERINE SMOOTH MUSCLE EXCITABILITY Principal Investigator & Institution: Davy, Kevin P.; Physiology and Biophysics; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: Preterm births account for only 10 percent of all deliveries, but are associated with over 80 percent of newborn deaths and more than 95 percent of major newborn morbidity. The lack of understanding of the mechansims regulating uterine contraction has hampered progress towards an effective treatment for this reproductive health problem. Currently used tocolytics have little effect in prolonging gestation, necessitating the investigation of other mechansims of prevention. One potential class of
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therapeutic targets is potassium channels, due to their ability to potently buffer cell excitation. Electrophysiological reports have shown that myometrial cells contain a variety of K+ channel types that may be potential therapeuric targets, including the large-conductance calcium-activated K+ channel (BKCa channel). Blockage of BKCa channels depolarizes myometrial cells and increases contractile activity while activation of these channels by agonists and beta-adrenergic agents induces potent uterine relaxation. Interestingly, the activation of the BKCa channel by phosphorylating agents, Ca2+, or voltage is dependent on whether it is isolated from non-pregnant or pregnant tissue. Recent evidence illustrates the ability of this channel to undergo alternative splicing in the presence of stress hormones, yielding variants that differ in their sensitivity to intracellular Ca2+ and voltage. Sensitivity to these agents is also dependent on the association of the BKCa channel with its ancillary beta subunit. This suggests that alternative splicing or modulation of beta subunit association may be mechanisms regulating BKCa channel diversity in uterine smooth muscle during gestation. While this channel appears to be an important regulatory component of uterine excitability, its role in modulating myometrial contraction during gestation remains unknown. The specific objective of this proposal is to detemine whether modulation of BKCa channel splice variant expression or beta subunit association correlates to a functional difference in uterine excitability during gestation. Alterations in BKCa channel splice variant expression and function during gestation will be investigated by molecular charactization in combination with electrophysiological and contraction measurements in mice. The specific aims of this proposal are to: 1) compare transcript and protein expression patterns of BKCa channel isoforms in mouse uterine smooth muscle during gestaiton, 2) elucidate BKCa channel beta subunit transcript and protein expression during gestation and detemine whether its assembly with the alpha subunit is modulated during pregnancy, 3) determine the contribution of BKCa channel splice variants to the regulation of uterine smooth muscle contraction during gestation, and 4) characterize the expression of the splice variants of the BKCa channel alpha subunit following stimulation with estrogen and progesterone. Preterm labor is a major health problem, especially given the risks it carries with respect to birth defects and the costs associated with premature delivery. Whether the BKCa channel could be a future target for tocolytic drug therapy is thus a significant question to examine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATORY MECHANISMS OF CARDIAC REPOLARIZATION Principal Investigator & Institution: Tamkun, Michael M.; Professor; Physiology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-DEC-2001 Summary: (adapted from the applicant's abstract): Voltage-gated K+ channels, responsible for action potential repolarization and setting the resting membrane potential, are proteins encoded by one of the most complex group of ion channel genes found in the cardiovascular system. A small change in K+ permeability in vascular smooth muscle membranes, results in a significant change in membrane potential and in Ca2+ channel activity. Thus, changes in K+ channel function can have an important effect on vascular tone. Three specific aims will be examined in the proposed work. 1. K+ channel subunit localization and assembly will be analyzed in rat cardiac myocytes and vascular smooth muscle tissue. Two hypotheses will be examined: (i) In heart Kva1.5 is either a homomeric alpha structure or assembled with Kva1.2 at the intercalated disk. In the ventricle (but not the atrium) the Kva1.5-containing complex is assembled with an inactivation-conferring Kvb subunit. (ii) In vascular smooth muscle,
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Kva1.5 exists as a heteromeric structure in association with the Kva1.4 subunit and the Kvb1.2 beta subunit. 2. The mechanisms underlying potassium channel a/b subunit interactions will be determined. Two hypotheses will be examined. (i) ab assembly involves the association of nascent channels with chaperon-like proteins that facilitate subunit assembly. (ii). Specific amino acids on b subunits determine physical ab interactions. The beta effects on voltage-sensitivity, deactivation, and inactivation can be traced to different amino acids. Furthermore all ab interactions occur at the N-terminal domains of both the alpha and beta subunits. 3. The cellular and subcellular distribution of the IKr potassium channel protein, h-erg, will be determined in normal and diseased human myocardium. One hypothesis will be investigated: IKr expression is not static, with localization being altered in diseased myocardium. The immunohistochemistry in aims 1 and 3 will be performed primarily on rat, canine and human tissue sections with antibodies that currently exist and antisera under production. Alpha-beta interactions will be monitored functionally by voltage-clamp techniques and physically by immunopurification. Subunit assembly will be determined by immunopurification methods where purification of two distinct subunits with an antibody specific for only one is the operational definition of assembly. The amino acids involved in this interaction will be identified by a variety of mutagenesis approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RENAL EFFECTS OF DIETARY CHLORIDE IN AFRICANAMERICANS Principal Investigator & Institution: Morris, R Curtis.; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2003 Summary: We recently reported that when dietary potassium was controlled at a marginally deficient intake not uncommon in many African- Americans (blacks), 30 mmol/d, salt sensitivity occurred in the majority of normotensive blacks but in relatively few normotensive Caucasian-Americans (whites), and on average was more severe in blacks. In a subsequent study of normotensive and mildly hypertensive black men consuming a diet marginally deficient in potassium, we observed that in those who were salt- sensitive, dietary NaCl loading induced a renal vasoconstrictive dysfunction in which renal blood flow (RBF) decreased, renal vascular resistance (RVR) and filtration (FF) increased, and glomerular filtration rate trended upward. The changes in mean arterial pressure induced by dietary NaCl varied inversely with those induced in RBF and directly with those in RVR and FF. In those blacks who were not salt-sensitive, renal dysfunction was not observed with NaCl loading. Since dietary loading of sodium citrate (and other non-Cl sodium salts) fails to induce a pressor response in patients with salt-sensitive hypertension, sodium citrate might also fail to induce a renal vasoconstrictive dysfunction in normotensive salt-sensitive blacks. We anticipate this finding, and will interpret it as evidence suggesting that the pressor effect induced in blacks by NaCl loading requires the induction of a renal vasoconstrictive dysfunction, which in turn requires the Cl- component of loaded NaCl. We have recently reported that in the stroke-prone spontaneously hypertensive rat fed a normal NaCl diet, supplemental KCl induced a persisting exacerbation of hypertension, renal vasculopathy and strokes, whereas supplemental KHCO3 had opposite effects. When this rat was NaCl-loaded, supplemental KCl, but not KHCO3, further exacerbated hypertension and the renal vasculopathy, increased the frequency of strokes, and within hours induced a reduction in urinary creatinine excretion. In normotensive and mildly hypertensive blacks fed a normal NaCl diet (150mmol/d) just adequate in potassium
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(45 mmol/d), we will determine whether KCl and K-citrate (100 mmol/d) supplemented for 14 days have differing pressor and renal hemodynamic effects. We anticipate that both supplemented potassium salts will induce a decrease in blood pressure, but that a lower RBF and a higher RVR and FF will attend supplemental KCl. We will interpret such findings as suggesting that the Cl component of KCl can exert a renal vasoconstrictive and potentially renopathic effect despite a concomitant decrease in blood pressure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RENAL POTASSIUM TRANSPORT IN PHYSIOLOGY AND DISEASES Principal Investigator & Institution: Huang, Chou-Long L.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2002 Summary: (Adapted from the Applicant's Abstract): Potassium channels play essential roles in the regulation of fluid and electrolyte transport in kidney. cDNAs for the renal potassium channel ROMKI and its isoforms ROMK2 and 3 have been isolated. Dysfunction of the potassium channels is one of the genetic causes for Bartter's syndrome. Our long-term objectives are to understand the molecular composition of the renal potassium channels, the regulation of the potassium channels by dietary potassium intake and by hormones, the structural elements of the channel for regulation by phosphatidylinositol 4.5-bisphosphate (PIP2), and the molecular basis for channel dysfunction in Bartter's syndrome. Potassium channels in kidney may consist of heteroand/or homo-multimers of ROMK isoforms with or without accessory proteins cystic fibrosis transmembrane regulator (CFTR). The molecular composition of the renal potassium channels will be studied using immunohistochemical co-localization and coimmunoprecipitation of rat kidney tissue. The stoichiometry of ROMK multimers and of ROMK-CFTR interaction will be examined by FPLC gel-filtration chromatography and sucrose-density centrifugation. Rats will be maintained in control or high potassium diets for 2 weeks to examine the effect of dietary potassium intake on ROMK expression. To determine the role of aldosterone in the regulation of ROMK expression by high potassium intake, rats will be adrenalectomized and maintained in control or high potassium diet with or without aldosterone replacement. The structural elements of ROMK involved in the regulation by PIP2 will be examined by expression studies in Xenopus oocytes. The positively charged residues in the cytoplasmic domain of ROMK will be replaced by glutamine. Mutant channels will be expressed in oocytes and studied by giant excised inside-out patches for regulation by PIP2. The intracellular processing and maturation of the natural mutant channels of Bartter's syndrome will be studied by pulse-chase experiments in cultured cells and by in vitro translation in pancreatic microsomes. The structural and functional constraints conferred by Bartter's mutation will be examined by screening libraries of ROMK constructed by saturation mutagenesis in a potassium uptake-defective yeast strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELECTIVE SUBPOPULATIONS
ACTIVATION
OF
DOPAMINE
RECEPTOR
Principal Investigator & Institution: Mailman, Richard B.; Professor; Neuroscience Center; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599
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Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-DEC-2002 Summary: (Adapted from applicant's abstract): The foundation of this FIRST Award is the testing of a novel concept termed the "functional selectivity hypothesis." It posits that the interaction of "atypical" drugs with a single G-protein receptor isoform may cause functional effects as extreme as agonist vs. antagonist (depending on the nature of the involved G-proteins and the type of conformational changes induced by drugreceptor interaction). While this hypothesis is proposed to generalize to all G-protein coupled receptor systems, I propose to test and refine this hypothesis by studying D2like dopamine (DA) receptors. The first data in support of this notion were result showing that novel hexahydrobenzo.a.phenanthridine dopaminergic ligands [i.e., dihydrexidine (DHX) and its analogs] activated post-synaptic, but not pre-synaptic, D2like receptors. The current application will focus on mechanistic studies that can provide a firm underpinning for the underlying "functional selectivity hypothesis." The working hypothesis is that DHX and its N-n-propyl analog have full agonist actions at those D2like receptors coupled to adenylate cyclase, whereas as these drugs are antagonists (or low efficacy partial agonists) at D2 receptors linked to potassium channels. Both DHX and N-p-DHX cause robust inhibition of adenylate cyclase in several models (e.g., inhibition of forskolin-stimulated or D1-mediated cCAMP synthesis/efflux in striatum, pituitary lactotrophs, or D2-transfected C-6 and MN9D clonal cells). Surprisingly, however, these same drugs have little or no effect on D2 receptors known (or presumed) to be coupled to potassium (K+) channels (e.g., they do not inhibit dopamine cell firing or dopamine release, and they induce only weak activation of K+ channels in pituitary lactotrophs). The development of drugs (such as the hexahydrobenzo[a]phenathridines) with functional selectivity may lead to dramatically improved pharmacotherapies by providing opportunities for targeting a subset of receptor-linked events, thus avoiding the undesirable side effects due to widespread activation or blockade of receptor functions. Such drugs would provide "pharmacological scalpels" for perturbing selected aspects. To begin to elucidate the mechanisms of functional selectivity, my experiments will focus on the actions of DHX on D2 receptor functions in rat striatum. The first aim is to collect concentration/response data to determine the potencies and efficacies of DHX and analogs at D2 receptors linked to adenylate cyclase or K+ channels. Superfused striatal slices will be used to compare effects on Da and ACh release (reflecting ion channel activation) with effects on cAMP efflux (an index of adenylate cyclase activation). Autoreceptor-mediated actions on adenylate-cyclase linked DA synthesis will be assessed by kinetic analysis of tyrosine hydroxylase. Aim 2 will extend results from in vitro studies to two in vivo paradigms, cerebral microdialysis (to measure DA, ACh and cAMP overflow) and the gamma-butyrolactone (GBL) model (to measure effects on DA synthesis). Experiments in Aim 3 will compare the pattern of Gprotein activation by DHX and typical D2 agonists. Agonist-induced binding of [alpha32P]GTP to G-proteins isoforms in striatal membranes and MN9D cells will be used as a marker of G-protein activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SENSORY PROCESSING IN THE VESTIBULAR ORGANS Principal Investigator & Institution: Eatock, Ruth; Assistant Professor; Otorhinolaryn & Communica Scis; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-1994; Project End 31-MAR-2002 Summary: The long-term goal of this work is to understand how vestibular organs, which transduce head position and movement, function and develop. Good health depends on the normal function of these organs. Damage can lead to debilitating
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vertigo, dizziness and an inability to maintain steady gaze. The primary afferent neurons to vestibular organs vary in the sensitivity and time course of their responses to head movement stimuli. Some of the variation correlates with region within the sensory organ. In amniotes, a further source of variation is likely to be differences between two classes of sensory hair cell, type I and II. This application proposes to take three approaches to stimulus processing by mammalian vestibular organs, using the rodent utricle as a model. The first aim is to test whether there are regional and cell-typespecific differences in the properties of the hair cell's mechanosensitive transducer conductance, which converts head movement stimuli into the receptor potential. Second, the hair cells' voltage-gated potassium conductances, which shape the receptor potential, will be characterized at the molecular level by applying probes directed at candidate proteins and messenger RNA. These conductances differ substantially between type I and II hair cells. The third aim is to characterize the normal development of hair cells from the period of peak terminal mitoses (prenatal) to birth of the animal. At birth, mouse utricular hair cells express some voltage-gated conductances and ultrastructural analysis shows that although the utricle is immature in many ways, some cells can be recognized as type I or II. The prenatal time course of acquisition of voltagegated conductances will be determined with whole-cell recording. The expression of voltage-gated potassium channel proteins will be followed in time with molecular probes. Prenatal morphological differentiation of the utricle will be characterized. These experiments should provide insight into early differentiation of hair cells and supporting cells, as well as determine the utility of potassium channel proteins as markers of hair cell differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SIGNALLING WITHIN THE DROSOPHILA SEGMENTAL NERVE Principal Investigator & Institution: Stern, Michael; Biochemistry and Cell Biology; Rice University 6100 S Main Houston, Tx 77005 Timing: Fiscal Year 2001; Project Start 08-FEB-2001; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract) Proper function of the nervous system requires specific interactions between neurons and glia, and yet the precise mechanisms by which these interactions occur remain incompletely understood. The Drosophila segmental nerve, which comprises a layer of motor and sensory axons surrounded by an inner (peripheral) and outer (perineural) glial layer, provides a genetic system for the analysis of this intercellular signaling. Mutations in push, a gene identified and cloned in the PI's lab, and Nf1, the Drosophila homolog of the gene responsible for neurofibromatosis in humans, each increase the thickness of the perineural glial layer. In addition, the effect of push and Nf1 mutations are strongly potentiated by mutations in ine which encodes a neurotransmitter transporter. The effect of push mutations in perineural glial growth is also enhanced by mutations in eag which encodes a potassium channel subunit. Both push and Nf1 encode intermediates in the receipt of intercellular signaling pathways mediated by the PACAP neuropeptide, or by the amnencoded protein, which is PACAP-related. Thus their results are consistent with a model in which perineural growth in Drosophila is controlled by two interacting neurotransmitter-mediated signaling pathways, one controlled by Amn and acting through push and Nf1, and the second controlled by substrate neurotransmitter of ine and acting through eag. The PI proposes a further dissection of these intercellular signaling pathways. Three specific questions are asked. First, is the Amn signal released from peripheral glia and received by perineural glia or is the signal released from neurons, received by peripheral glia and then signaled by a relay mechanism to
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perineural glia? Second, does the Eag potassium channel act in the Amn signaling cell, or in the Amn receiving cell, to modulate the effect of Amn signaling on perineural growth? Third, in other PACAP or Amn signaling pathways described, additional intermediates have been implicated, including PKA, Ras and Raf. Which of these intermediates participate in Amn signaling in the Drosophila segmental nerve? These experiments will provide new molecular insights into the nature of neuron/glia signaling. In addition, it appears that defects in signaling with this pathway models, at least in part, the tumor formation that occurs in neurofibromatosis. Thus the studies proposed here are anticipated to enable the development of new models for the role of Nf1 in tumor formation, and perhaps enable the development of new pharmacological strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMALL CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNELS Principal Investigator & Institution: Adelman, John P.; Senior Scientist; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 03-AUG-1998; Project End 31-JUL-2002 Summary: Small conductance calcium-activated potassium channels (SK channels) serve a fundamental role in excitable cells. Activated by elevated levels of intracellular calcium, SK channels mediate the slow after hyperpolarization, the sAHP, which follows the action potential spike. During a sustained stimulus, a train of action potentials is elicited and the depth and extent of the sAHP are increased with each action potential such that the cell is ultimately unable to fire a subsequent action potential even though the stimulus to fire remains. This phenomenon is termed 'spike-frequency adaptation' and protects the cell from tetanic stimulation and associated cell toxicity. Subtypes of SK channels may be distinguished by different sensitivities to the bee venom peptide toxin apamin. Application of apamin to regions of the brain alters physiologically important processes, such as sleep patterns and learning and memory. While the sAHP in most neurons is apamin-sensitive, in some neurons such as hippocampal pyramidal cells, the sAHP is apamin-insensitive, shows a slower time course, and is modulated by activation of protein kinase A (PKA). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECTROSCOPIC STUDIES OF ENZYME/SUBSTRATE COMPLEXES Principal Investigator & Institution: Reed, George H.; Professor; Institute for Enzyme Research; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JAN-1986; Project End 31-DEC-2002 Summary: The objectives of the project are to gain a better understanding of the mechanisms of enzymatic catalysis and of the means by which inorganic cations contribute to the catalytic processes. Pyruvate kinase and enolase, enzymes from the glycolytic pathway, are of central importance to carbohydrate metabolism in all living organisms. Both enzymes require specific activation by two equivalents of divalent cation, and pyruvate kinase requires activation by potassium as well. Each enzyme exhibits one or more instances of general acid-base catalysis during the catalytic cycle. The roles of magnesium and other divalent cations in enzymatic catalysis are poorly understood. General acid-base catalysis is a topic of current interest in enzymology. Studies of enolase and pyruvate kinase hold promise for revealing fundamental concepts in these areas. The specific aims of the project focus on key aspects of activation
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by metal ions and of general acid-base catalysis that have been revealed in previous studies. X-ray crystallography, site-directed mutagenesis, spectroscopic, and kinetic methods are proposed to approach the specific aims which include experiments to: 1) determine the pKa's of the general acid-base catalysts in the active site of enolase; 2) probe the basis for metal specificity in the steps of enolase catalysis; 3) correlate structure and function of wild type and site specific mutant enolases; 4) search for the group or groups responsible for general acid-base catalysis and for a potential proton relay network in the active site of pyruvate kinase; 5) probe the structural outcome of a Glu to Lys mutation in pyruvate kinase that eliminates the requirement for activation by potassium and probe the structural changes induced by an allosteric effector. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPINAL NEURAL ACTIVITY--ROLE IN POST ISCHEMIC INJURY Principal Investigator & Institution: Marsala, Martin; Anesthesiology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract) This revised renewal proposal is to investigate the mechanisms by which certain interventions protect against the cascade of deleterious events that follow a period of spinal ischemia. There are two specific aims. The first is to define the optimal thermal and temporal characteristics of perischemic cooling. Measures of ischemic consequences or correlative changes with protection include spinal extracellular potassium, dorsal horn neuronal activity, amino acid and PGE2 release, neurological outcome at 2-5 days and spinal histopathology. The second aim is to define the factors governing spinal expression of HSP72 and immediate early genes, and the correlation of such expression with post-ischemia functional recovery. hsp72, c-fos and c-jun expression will be measured following transient cooling or heating to two different temperatures, intrathecal delivery of substance P; NMDA, AMPA, or kainic acid; high potassium; or either of two transient non-injurious intervals of spinal ischemia. The protective effects of these manipulations will be measured on damage observed with a fixed injurious duration of ischemia delivered at 3 different intervals after the conditioning treatments which induce hsp72 and/or fos/jun expression; measures of damage include neurologic outcome, spinal amino acid and PGE2 release and histopathology. The role of HSP72 expression in protection will be tested by examining the effects of antisense pretreatment on HSP72 expression and the same three measures of ischemic damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURAL ANALYSIS OF VOLTAGE-GATED POTASSIUM CHANNELS Principal Investigator & Institution: Blaustein, Robert O.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Potassium channels are specialized integral membrane proteins endowed with a remarkable capacity to accommodate the highly selective passage of potassium ions across cells. Some have the added ability to open and close in response to small changes in transmembrane voltage, and it is these voltage-gated (Kv) potassium channels that are the focus of this proposal. These proteins play crucial roles in a number of physiologic processes ranging from the propagation of information in the nervous system to the maintenance of a normal heart
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rhythm, and inherited mutations in many of them lead to forms of epilepsy, paralysis, and cardiac arrhythmias. The structures of some parts of Kv channels and their auxiliary subunits are now well understood, yet despite detailed study for over a decade, little is known about the construction of the voltage sensing region of these channels, or about the overall architecture of hetermultimeric channels. In light of this gap, a new method is introduced to complement established techniques of molecular biology and electrophysiology--the use of tethered quaternary ammonium blockers as molecular tape-measures. These compounds will be targeted to intracellular and extracellular regions of two classes of K+ channels: the prototypic voltage-dependent Shaker channel, and heteromultimeric channels formed from the co-assembly of Shaker-like subunits with minK-related peptides (MiRPs). The two specific aims, (1) mapping the extracellular portion of Shaker's gating module, and (2) probing the structure of MiRPassociated channels, will be instrumental in fulfilling the project's long-term objectives of creating a detailed physical map of the gating module of a Kv channel, and determining how the different parts of a Kv channel are molded together. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND FUNCTION OF K+ CARRIER-CHANNELS IN YEAST Principal Investigator & Institution: Slayman, Clifford L.; Cellular/Molecular Physiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: The long-term goal of these experiments is to understand the molecular mechanisms of potassium accumulation in the yeast Saccharomyces cerevisiae, and the means by which intracellular potassium is regulated homeostatically. The experiments are prompted by the recent discovery that the two main transporter proteins involved, products of the TRK! and TRK2 genes, are sequence-similar to a major class of bacterial potassium channels. This finding has led to development of atomic scale-models for the two proteins (S.R. Durell & H.R. Guy; Biophysical Journal 77: 789-807, 1999) based on the crystal structure of one potassium channel, KcsA from $treptomyces lividans. The experiments will use yeast genetics/molecular biology to make several series of sitedirected mutations in the TRK1 and TRK2 genes, in order to test predictions of these "quasi-channel" structural models, in regard to the organization of trans-membrane topology (folding), location of potassium affinity and selectivity, location of a postulated co-ion pathway through the proteins, and intra-molecular salt-bridge formation. Functional assays will make use of recently refined techniques for membrane patch-recording in yeast (Bertl et al.; Europ. J. Physiol. 436:999, 1998), along with several types of ion-flux assays on intact yeast cells and protoplasts. The transport systems involved are thought to be H+-K+ cotransporters (symporters), functionally resembling many proton- or sodium- coupled substrate transporters in the so-called 12-TM class of molecules, found in all the biological kindgoms. But their peculiar sequence/structure suggests that their detailed mechanism of "active" transport may differ in fundamental ways from that of the more familiar proteins. Because these proteins are native to fungi, but thus far not to animal systems, they offer the possibility for design of fungal-specific antibiotics having few or no side effects, on human tissues for example. And because they appear to have a quasi-channel structure and some rather strange properties for ion-cotransporters (Bihler et al., FEBSLetters 447:115-120), they may shed light on the important phenomenon of alternative carder and channel function in certain neurotransmitter transport systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE OF ATP SENSITIVE POTASSIUM CHANNELS Principal Investigator & Institution: Bryan, Joseph; Professor; Cell Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-MAR-2002 Summary: (Adapted from the investigator's application): ATP-sensitive K+ channels, KATP, can be reconstituted from SUR1, a member of the ATP-binding cassette superfamily and KIR6.2, a member of the inward rectifier K+ channel family. The reconstituted channel is a moderate inward rectifier whose conductance is appropriately modulated by ATP/ADP, by sulfonylurea channel blockers and potassium channel openers. Preliminary data suggest SUR1 and KIR6.2 assemble with a 1:1 stoichiometry into large complexes, presumably KATP channels. The overall objective of the application is to test the hypothesis that KATP channels have a tetrameric architecture, (SUR1/KIR6.2)4. The specific objectives are: 1) To establish that SUR1 and KIR6.2 associate to form a heteromultimeric complex. Association is being monitored using histagged SUR1 and KIR6.2 subunits, by utilizing specific lectins that bind SUR1, by cophotolabeling with 125I-azidoglibenclamide and by the appearance of a complex glycosylation pattern of SUR1. 2) To determine the stoichiometry of the complex. This is being done using sedimentation velocity measurements to estimate the molecular size(s) of the complexes and by engineering and expressing active channel forming fusion proteins with defined stoichiornetries, e.g., SUR1-KIR6.2 and SUR1-(KIR6.2)2. 3) To determine the stoichiometry of active KATP channels. This is being done using a mutant of KIR6.2, N 160D, that confers strong rectification on reconstituted KATP channels. Coexpression of wildtype KIR6.2 with the N 160D mutation gives heteromeric channels whose properties, along with SUR1-N160D fusion channels, will be used to determine if active channels are tetrameric. 4) To start to map the domains of interaction between SUR1 and KIR6.2. This is being done by engineering KIR6.2/KIR3.4 chimeras to determine which parts of KIR6.2 are needed for association and which for formation of active channels. KIR3.4 is similar to 6.2, but does not associate or form active channels with SUR1. This work will provide a model for ion channel regulation by members of the ATP-binding cassette superfamily. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUBCELLULAR DISTRIBUTION OF CARDIAC K CHANNELS Principal Investigator & Institution: Koren, Gideon; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (adapted from the applicant's description): Voltage-gated potassium channels play an important role in regulating cardiac cell excitation. A high incidence of cardiac arrhythmia is observed in patients with long QT syndrome, a disease caused by mutations in genes that encode voltage-gated potassium and sodium channels in the heart. The applicant has created a mouse model for long QT syndrome in which the expression of a potassium channel, Kv1.5, is markedly reduced. The purpose of this proposal is to study the mechanisms that regulate voltage-gated potassium channel polypeptide trafficking, targeting and expression in the membrane of cardiac cells. The applicant proposes to identify and characterize the proteins that are important for clustering and assembly of some submembranous macromolecular complexes that bind potassium channels. This knowledge will be used to create chimeric potassium channels and study their expression and subcellular targeting in vivo using transgenic mice as well as in vivo gene expression using adeno- and adeno-associated viral vectors.
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The effect of expression of exogenous potassium channels will be studied using voltageclamp analysis of single cells. Recording of QT interval and spontaneous arrhythmias in conscious mice, and analysis of inducible arrhythmias by programmed ventricular stimulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SUBCELLULAR LOCALIZATION OF NEURONAL ION CHANNELS Principal Investigator & Institution: Arnold, Donald B.; Biological Sciences; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The long-term goal of this research is to understand the molecular mechanisms involved in intracellular transport and localization of voltage-gated potassium channels. Specifically, peptide motifs within the primary amino acid structure of potassium channels that specify localization to the axon or to the dendrite will be identified. The role of interacting proteins that are involved in localization of potassium channels will also be studied. Biolistic transfection will be used to express proteins in cultured brain slices, enabling their subcellular localization to be visualized in neurons in a wild-type environment. Chimeras composed of a potassium channel that localizes to the axon and another that localizes to the dendrite, as well as deletion mutants of each channel will be tested in this assay to map regions responsible for axonal and dendritic localization. The assay will also be used to study the role of interacting proteins in subcellular localization of K+ channels. The first aim of this proposal is to investigate mechanisms by which potassium channels are specifically localized to axonal and dendritic compartments of neurons. Aim 2 is to investigate the role in localization of proteins that are known to interact with potassium channels and to identify additional interacting proteins using the yeast two-hybrid method. The electrical properties of excitable cells are highly dependent on voltage-gated potassium channels. Potassium channels have been implicated in diseases associated with impaired control of excitability such as epilepsy. While the physiology of individual potassium channels is relatively well understood at the molecular level, the question of how a cell distributes these channels along its membrane to produce an overall pattern of electrical activity is not known. Understanding of how the cell regulates ionic currents by altering the subcellular distribution of ion channels could lead to novel avenues of pharmaceutical intervention in neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THEORY OF SOLUTE AND WATER TRANSPORT ACROSS EPITHELIA Principal Investigator & Institution: Weinstein, Alan M.; Professor of Medicine and Physiology; Physiology and Biophysics; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-AUG-1981; Project End 31-JAN-2006 Summary: A mathematical model of the mammalian distal nephron will be developed, comprised of cellular models of ascending Henle limb, distal tubule, and collecting duct. The model will represent sodium, potassium, and acid/base transport under normal and pathological conditions, and will predict renal excretion from distal delivery. The project begins with models of the three collecting duct segments; it will require development of two distal tubule segments plus an ascending limb, and then concatenation of all segments into a distal nephron. The segmental models will
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incorporate representations of specific membrane transporters: in distal tubule, the NaCI cotransporter, and in ascending limb, the luminal Na-K-2CI and peritubular K-CI cotransporters. Segment-specific issues, as well as segmental interactions will be considered. For the collecting duct, proposed lesions underlying distal renal tubular acidosis (ATPase failure, base-exit defects, or paracellular leak) will be examined, and clinical tests for identifying these lesions will be simulated. In this, the objective is to examine the rationalization for the clinical taxonomy of distal tubular acidosis. The distal tubule model will be used to examine flow- dependence of potassium secretion, to estimate the component attributable to luminal gradient attenuation. This will be preliminary to quantifying the alkalinizing and potassium-wasting effect of thiazide diuretics, which act on distal tubule. In the ascending limb, an important focus will be identifying the modulated transporters responsible for cellular homeostasis, specifically, mechanisms used to accommodate large reabsorptive fluxes of sodium and ammonium, while preserving cell volume and pH. In ascending limb, the three different transport defects which all present as Bartter's syndrome will be simulated, to understand the potassium depletion alkalosis common to all three. The full distal nephron model will be required to critically examine the proposal that medullary interstitial potassium concentration modulates overall renal potassium and acid excretion: namely, that by blunting ascending limb sodium reabsorption, peritubular potassium sends more sodium to distal tubule and collecting duct where potassium secretion and base reabsorption depend on sodium delivery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSMISSION ACROSS FIRST SYNAPSE OF THE BAROREFLEX Principal Investigator & Institution: Andresen, Michael C.; Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-FEB-1991; Project End 31-MAR-2005 Summary: (the applicant's description verbatim): The autonomic nervous system contributes importantly to the homeostatic regulation of the heart and blood vessels through arterial baroreflexes and yet our understanding of the central nervous system mechanisms is limited. The sensory synapse of baroreceptors in the nucleus tractus solitarius (NTS) is unique since its participation is obligatory in the baroreflex. Our Research Plan targets this synapse to provide greater understanding of the cellular mechanisms at the earliest stages of the baroreflex. To best approach the cellular mechanisms operating in NTS, we have developed unique in vitro approaches incorporating dye labeling of aortic baroreceptors together with imaging and intracellular electrophysiology to assay synaptic transmission at single neurons under controlled conditions. Our new technical approach allows us to visualize and patch record from NTS neurons with. fluorescently labeled aortic baroreceptor boutons. Isolated, dispersed NTS neurons with attached sensory synaptic boutons will be studied to isolate ionic currents and signal transduction mechanisms in parallel experiments. The major long term goal is to test the hypothesis that this sensory synapse within NTS is the site of major transformation of sensory information. This work will focus on the synapse (pre- and postsynaptic elements) as well as potassium currents of the postsynaptic NTS neurons. Aims will examine the role of non-glutamatergic mediators in frequency dependent sensory synaptic depression, the presynaptic mechanisms modulating transmitter release, glutamate and GABA receptor interactions, potassium channels as a modulation target, and local inhibitory feedback interactions within NTS. Together, these Aims will provide new and direct information about the mechanisms of
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central nervous system integration and information processing of arterial baroreceptors at first stage of cardiovascular regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASCULAR SURGERY - ESTROGEN AND THE INJURY RESPONSE Principal Investigator & Institution: Mendelsohn, Michael E.; Professor; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 15-JAN-1997; Project End 31-MAR-2007 Summary: (provided by applicant): This is a competitive renewal application that focuses on the specific roles of estrogen receptors in vascular biology, with substantial significance for the surgical ischemic cardiovascular diseases. Using molecular approaches and transgenic mouse models, the present application focuses on the exciting new findings that both male and female estrogen receptor beta (ERbeta) knockout mice (ERbetaKO), as compared to their WT littermates, have vascular contractile abnormalities, marked reduction in vascular smooth muscle cell (VSMC) potassium currents, and progressive hypertension as they age. Substantial preliminary data are presented to support that this is related to ERbeta regulation of both the VSMC gene for inducible nitric oxide synthase (iNOS) and VSMC potassium channel genes. This application therefore tests the hypothesis that ERbeta is a critical determinant of normal vascular function and blood pressure through regulated expression of the iNOS gene and VSMC ion channel genes involved in VSMC contractile function. Three specific Aims are proposed: SA A studies the Mechanism of ERbeta-iNOS regulation of vascular tone in intact vessels using pharmacological inhibitors of ERs and iNOS in vascular rings of carotid arteries and intact mesenteric arteries from WT, ERalphaKO and ERbetaKO mice. The role of transcription and post-transcriptional regulation in the estrogen effect on contraction are tested, as is whether postnatal inhibition of ERbeta prevents the development of hypertension and/or postnatal removal of ERalpha actions prevents or modifies the development of hypertension. SA B uses cellular and in vitro approaches to identify the transcriptional mechanism of iNOS activation by ERbeta with transient transfection assays and electrophoretic mobility shift assays (EMSA), and yeast one-hybrid screening to identify VSMC-specific DNA binding proteins and transcriptional coactivators important to ERbeta-mediated iNOS induction. SA C examines which potassium channel genes are dysfunctional in the hypertensive ERbetaKO mice using specific pharmacological inhibitors in whole-cell patch clamping studies, and protein and mRNA expression studies in primary VSMC from ERbetaKO mice and their WT littermates. These studies are expected to add substantially to our understanding of vascular regulation by estrogen and estrogen receptors and to enhance further the academic vascular surgery-training environment at our institution. Furthermore, understanding the functional importance of estrogen receptors in the vasculature for blood pressure regulation may help in the design of specific therapies for the prevention and treatment of a variety of cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VOLTAGE DEPENDENT ION CHANNELS IN PURKINJE NEURONS Principal Investigator & Institution: Bean, Bruce P.; Professor; Neurobiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-MAY-2002 Summary: Neurons in the mammalian brain possess a rich variety of voltage-dependent ion channels, but there has been little detailed analysis of how particular ion channels
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work together to regulate the firing patterns of mammalian central neurons. In part, this has been due to limitations in voltage-clamping central neurons, especially for studying the large voltage-activated currents that flow during the action potential. The goal of the proposed research is to understand how the distinctive firing properties of cerebellar Purkinge neurons are produced by particular ion channels. The work is based on using a preparation of dissociated Purkinje neurons that allows a high-quality voltage-clamp of voltage- activated currents. Preliminary data show that the dissociated cells retain two of the distinctive firing properties of Purkinje cells in vivo, spontaneous firing and formation of complex action potentials. The experimental design will combine current clamp recordings of action potential firing with a voltage-clamp analysis of the voltagedependent sodium, potassium, and calcium channels that underlie the action potentials. Voltage clamp experiments will use ionic substitution and specific channel blockers, especially peptide toxins, to distinguish the contributions of particular channel types to the overall sodium, calcium, and potassium currents. Action potential waveforms will be used as command voltages to determine the contribution of particular ion channels to firing patterns. A particular focus will be to characterize a novel repolarization-gated sodium current using single channel and whole-cell recordings, and to understand the role of the current in spontaneous firing and in the formation of multi-spike action potentials. Understanding the mechanisms involved in regulating the electrical excitability of central neurons will help in understanding the normal function of the nervous system as well as pathophysiological states resulting form stroke, intoxication, and epilepsy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “potassium” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for potassium in the PubMed Central database: •
A functional role for the two-pore domain potassium channel TASK-1 in cerebellar granule neurons. by Millar JA, Barratt L, Southan AP, Page KM, Fyffe RE, Robertson B, Mathie A.; 2000 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16288
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A human intermediate conductance calcium-activated potassium channel. by Ishii TM, Silvia C, Hirschberg B, Bond CT, Adelman JP, Maylie J.; 1997 Oct 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23567
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits. by Cui Y, Giblin JP, Clapp LH, Tinker A.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14656
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A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors. by Nitabach MN, Llamas DA, Araneda RC, Intile JL, Thompson IJ, Zhou YI, Holmes TC.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14652
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A Mutation in the Arabidopsis KT2/KUP2 Potassium Transporter Gene Affects Shoot Cell Expansion. by Elumalai RP, Nagpal P, Reed JW.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150555
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A new approach to overcome potassium-mediated inhibition of triplex formation. by Svinarchuk F, Cherny D, Debin A, Delain E, Malvy C.; 1996 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146176
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A Novel Mechanism of Ion Homeostasis and Salt Tolerance in Yeast: the Hal4 and Hal5 Protein Kinases Modulate the Trk1-Trk2 Potassium Transporter. by Mulet JM, Leube MP, Kron SJ, Rios G, Fink GR, Serrano R.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84126
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Activation and inhibition of G protein-coupled inwardly rectifying potassium (Kir3) channels by G protein [beta][gamma] subunits. by Lei Q, Jones MB, Talley EM, Schrier AD, McIntire WE, Garrison JC, Bayliss DA.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16940
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Activation of Kv3.1 channels in neuronal spine-like structures may induce local potassium ion depletion. by Wang LY, Gan L, Perney TM, Schwartz I, Kaczmarek LK.; 1998 Feb 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19207
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Activation of Potassium Channels: Relationship to the Heat Shock Response. by Saad AH, Hahn GM.; 1992 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50138
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Activation of the potassium uptake system during fermentation in Saccharomyces cerevisiae. by Ramos J, Haro R, Alijo R, Rodriguez-Navarro A.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205809
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Alteration of intracellular potassium and sodium concentrations correlates with induction of cytopathic effects by human immunodeficiency virus. by Voss TG, Fermin CD, Levy JA, Vigh S, Choi B, Garry RF.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190502
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Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome. by Arrighi I, Bloch-Faure M, Grahammer F, Bleich M, Warth R, Mengual R, Drici MD, Barhanin J, Meneton P.; 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37514
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Ammonium inhibition of Arabidopsis root growth can be reversed by potassium and by auxin resistance mutations aux1, axr1, and axr2. by Cao Y, Glass AD, Crawford NM.; 1993 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158872
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An Arabidopsis mutant that requires increased calcium for potassium nutrition and salt tolerance. by Liu J, Zhu JK.; 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25145
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An overview of the potassium channel family. by Miller C.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138870
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AtKC1, a silent Arabidopsis potassium channel [alpha]-subunit modulates root hair K + influx. by Reintanz B, Szyroki A, Ivashikina N, Ache P, Godde M, Becker D, Palme K, Hedrich R.; 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122651
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AtKUP1: an Arabidopsis gene encoding high-affinity potassium transport activity. by Kim EJ, Kwak JM, Uozumi N, Schroeder JI.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=143935
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Basolateral membrane targeting of a renal-epithelial inwardly rectifying potassium channel from the cortical collecting duct, CCD-IRK3, in MDCK cells. by Le Maout S, Brejon M, Olsen O, Merot J, Welling PA.; 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24308
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Better conditions for mammalian in vitro splicing provided by acetate and glutamate as potassium counterions. by Reichert V, Moore MJ.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102525
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Cerebellar neurons lacking complex gangliosides degenerate in the presence of depolarizing levels of potassium. by Wu G, Xie X, Lu ZH, Ledeen RW.; 2001 Jan 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14586
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Cloning and characterization of a potassium-coupled amino acid transporter. by Castagna M, Shayakul C, Trotti D, Sacchi VF, Harvey WR, Hediger MA.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20272
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Cloning and Expression of a Rat Cardiac Delayed Rectifier Potassium Channel. by Paulmichl M, Nasmith P, Hellmiss R, Reed K, Boyle WA, Nerbonne JM, Peralta EG, Clapham DE.; 1991 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52410
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Cloning and Expression of Two Brain-Specific Inwardly Rectifying Potassium Channels. by Bredt DS, Wang T, Cohen NA, Guggino WB, Snyder SH.; 1995 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41407
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Collecting duct --specific gene inactivation of [alpha]ENaC in the mouse kidney does not impair sodium and potassium balance. by Rubera I, Loffing J, Palmer LG, Frindt G, Fowler-Jaeger N, Sauter D, Carroll T, McMahon A, Hummler E, Rossier BC.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=171384
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Controlling potassium channel activities: Interplay between the membrane and intracellular factors. by Yi BA, Minor DL Jr, Lin YF, Jan YN, Jan LY.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58676
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Crystallographic Evidence for the Action of Potassium, Thallium, and Lithium Ions on Fructose-1,6-Bisphosphatase. by Villeret V, Huang S, Fromm HJ, Lipscomb WN.; 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41078
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Cyclic AMP regulates potassium channel expression in C6 glioma by destabilizing Kv1.1 mRNA. by Allen ML, Koh DS, Tempel BL.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22725
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Defective regulatory volume decrease in human cystic fibrosis tracheal cells because of altered regulation of intermediate conductance Ca2 +-dependent potassium channels. by Vazquez E, Nobles M, Valverde MA.; 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33209
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Desensitization of [mu]-opioid receptor-evoked potassium currents: Initiation at the receptor, expression at the effector. by Blanchet C, Luscher C.; 2002 Apr 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123706
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Determination of transmembrane topology of an inward-rectifying potassium channel from Arabidopsis thaliana based on functional expression in Escherichia coli. by Uozumi N, Nakamura T, Schroeder JI, Muto S.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21412
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Distinct Abscisic Acid Signaling Pathways for Modulation of Guard Cell versus Mesophyll Cell Potassium Channels Revealed by Expression Studies in Xenopus laevis Oocytes. by Sutton F, Paul SS, Wang XQ, Assmann SM.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59137
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Divalent transition metal cations counteract potassium-induced quadruplex assembly of oligo(dG) sequences. by Blume SW, Guarcello V, Zacharias W, Miller DM.; 1997 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146479
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Dual mechanism for stimulation of glutamate transport by potassium ions in Streptococcus mutans. by Sato Y, Noji S, Suzuki R, Taniguchi S.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210304
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Dual system for potassium transport in Saccharomyces cerevisiae. by RodriguezNavarro A, Ramos J.; 1984 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215750
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Energy-linked potassium uptake by mitochondria from wild-type and poky strains of Neurospora crassa. by Smith EW, Slayman CW.; 1977 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235019
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Enterocin P Causes Potassium Ion Efflux from Enterococcus faecium T136 Cells. by Herranz C, Cintas LM, Hernandez PE, Moll GN, Driessen AJ.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90390
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Evidence for the existence of a sulfonylurea-receptor-like protein in plants: Modulation of stomatal movements and guard cell potassium channels by sulfonylureas and potassium channel openers. by Leonhardt N, Marin E, Vavasseur A, Forestier C.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28449
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Expression and Stress-Dependent Induction of Potassium Channel Transcripts in the Common Ice Plant. by Su H, Golldack D, Katsuhara M, Zhao C, Bohnert HJ.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64862
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Expression of an Atrial G-Protein-Activated Potassium Channel in Xenopus Oocytes. by Dascal N, Lim NF, Schreibmayer W, Wang W, Davidson N, Lester HA.; 1993 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46979
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Extracellular Protons Inhibit the Activity of Inward- Rectifying Potassium Channels in the Motor Cells of Samanea saman Pulvini. by Yu L, Moshelion M, Moran N.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129298
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Functions of AKT1 and AKT2 Potassium Channels Determined by Studies of Single and Double Mutants of Arabidopsis. by Dennison KL, Robertson WR, Lewis BD, Hirsch RE, Sussman MR, Spalding EP.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129271
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Genetic analysis of potassium transport loci in Escherichia coli: evidence for three constitutive systems mediating uptake potassium. by Dosch DC, Helmer GL, Sutton SH, Salvacion FF, Epstein W.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207060
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Genetic analysis of salt tolerance in arabidopsis. Evidence for a critical role of potassium nutrition. by Zhu JK, Liu J, Xiong L.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=144057
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Glutamate and 2-Amino-4-Phosphonobutyrate Evoke an Increase in Potassium Conductance in Retinal Bipolar Cells. by Hirano AA, MacLeish PR.; 1991 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50902
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Glutamate is Required to Maintain the Steady-State Potassium Pool in Salmonella typhimurium. by Yan D, Ikeda TP, Shauger AE, Kustu S.; 1996 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39057
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Glycine residues in potassium channel-like selectivity filters determine potassium selectivity in four-loop-per-subunit HKT transporters from plants. by Maser P, Hosoo Y, Goshima S, Horie T, Eckelman B, Yamada K, Yoshida K, Bakker EP, Shinmyo A, Oiki S, Schroeder JI, Uozumi N.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122965
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High-Affinity Potassium Transport in Barley Roots. Ammonium-Sensitive and Insensitive Pathways. by Santa-Maria GE, Danna CH, Czibener C.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59003
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High-affinity potassium uptake system in Bacillus acidocaldarius showing immunological cross-reactivity with the Kdp system from Escherichia coli. by Bakker EP, Borchard A, Michels M, Altendorf K, Siebers A.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213750
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Hypoxic pulmonary vasoconstriction: role of voltage-gated potassium channels. by Sweeney M, Yuan JX.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59541
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Identification of an Ancillary Protein, YabF, Required for Activity of the KefC Glutathione-Gated Potassium Efflux System in Escherichia coli. by Miller S, Ness LS, Wood CM, Fox BC, Booth IR.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94807
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Identification of osmoresponsive genes in Escherichia coli: evidence for participation of potassium and proline transport systems in osmoregulation. by Gowrishankar J.; 1985 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214263
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Induction of Apoptosis in Cerebellar Granule Neurons by Low Potassium: Inhibition of Death by Insulin-Like Growth Factor I and cAMP. by D'Mello SR, Galli C, Ciotti T, Calissano P.; 1993 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47907
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Interchain hydrogen-bonding interactions may facilitate translocation of K + ions across the potassium channel selectivity filter, as suggested by synthetic modeling chemistry. by Mareque Rivas JC, Schwalbe H, Lippard SJ.; 2001 Aug 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55477
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Intracellular accumulation of potassium and glutamate specifically enhances survival of Escherichia coli in seawater. by Gauthier MJ, Flatau GN, Le Rudulier D, Clement RL, Combarro Combarro MP.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182697
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Intrinsic flexibility and gating mechanism of the potassium channel KcsA. by Shen Y, Kong Y, Ma J.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122300
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Inventory and Functional Characterization of the HAK Potassium Transporters of Rice. by Banuelos MA, Garciadeblas B, Cubero B, Rodriguez-Navarro A.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166606
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Isolation and Properties of Enterococcus hirae Mutants Defective in the Potassium/Proton Antiport System. by Kakinuma Y, Igarashi K.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93903
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Lactococcin G is a potassium ion-conducting, two-component bacteriocin. by Moll G, Ubbink-Kok T, Hildeng-Hauge H, Nissen-Meyer J, Nes IF, Konings WN, Driessen AJ.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177700
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Lasalocid-catalyzed proton conductance in Streptococcus bovis as affected by extracellular potassium. by Schwingel WR, Bates DB, Denham SC, Beede DK.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184090
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Long QT and ventricular arrhythmias in transgenic mice expressing the N terminus and first transmembrane segment of a voltage-gated potassium channel. by London B, Jeron A, Zhou J, Buckett P, Han X, Mitchell GF, Koren G.; 1998 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19671
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Low-affinity potassium uptake system in Bacillus acidocaldarius. by Michels M, Bakker EP.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213749
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Low-affinity potassium uptake system in the archaeon Methanobacterium thermoautotrophicum: overproduction of a 31-kilodalton membrane protein during growth on low-potassium medium. by Glasemacher J, Siebers A, Altendorf K, Schonheit P.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177719
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Mechanism of High-Affinity Potassium Uptake in Roots of Arabidopsis thaliana. by Maathuis FJ, Sanders D.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44794
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Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase. by Shyng SL, Barbieri A, Gumusboga A, Cukras C, Pike L, Davis JN, Stahl PD, Nichols CG.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15434
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Muscarinic and [beta]-Adrenergic Depression of the Slow Ca2+- Activated Potassium Conductance in Hippocampal CA3 Pyramidal Cells is not Mediated by a Reduction of Depolarization-Induced Cytosolic Ca2+ Transients. by Knopfel T, Vranesic I, Gahwiler BH, Brown DA.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54051
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Opioid receptors from a lower vertebrate (Catostomus commersoni): Sequence, pharmacology, coupling to a G-protein-gated inward-rectifying potassium channel (GIRK1), and evolution. by Darlison MG, Greten FR, Harvey RJ, Kreienkamp HJ, Stuhmer T, Zwiers H, Lederis K, Richter D.; 1997 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21583
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ORK1, a potassium-selective leak channel with two pore domains cloned from Drosophila melanogaster by expression in Saccharomyces cerevisiae. by Goldstein SA, Price LA, Rosenthal DN, Pausch MH.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24080
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Osmotic regulation of transcription: induction of the proU betaine transport gene is dependent on accumulation of intracellular potassium. by Sutherland L, Cairney J, Elmore MJ, Booth IR, Higgins CF.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213556
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Outer Pore Residues Control the H+ and K+ Sensitivity of the Arabidopsis Potassium Channel AKT3. by Geiger D, Becker D, Lacombe B, Hedrich R.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151470
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Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression. by Sutherland ML, Williams SH, Abedi R, Overbeek PA, Pfaffinger PJ, Noebels JL.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26805
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Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. by D'hahan N, Moreau C, Prost AL, Jacquet H, Alekseev AE, Terzic A, Vivaudou M.; 1999 Oct 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18429
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Positively charged oligonucleotides overcome potassium-mediated inhibition of triplex DNA formation. by Dagle JM, Weeks DL.; 1996 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145908
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Potassium Channel Dysfunction in Fibroblasts Identifies Patients with Alzheimer Disease. by Etcheberrigaray R, Ito E, Oka K, Tofel-Grehl B, Gibson GE, Alkon DL.; 1993 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47318
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Potassium extrusion by the moderately halophilic and alkaliphilic methanogen methanolobus taylorii GS-16 and homeostasis of cytosolic pH. by Ni S, Boone JE, Boone DR.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=197116
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Potassium requirement for cell division in Anacystis nidulans. by Ingram LO, Thurston EL.; 1976 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=233372
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Potassium translocation in yeast mitochondria and its relationship to ergostrol biosynthesis. by Bailey RB, Parks LW.; 1975 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246098
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Potassium Transport and the Relationship Between Intracellular Potassium Concentration and Amino Acid Uptake by Cells of a Marine Pseudomonad. by Thompson J, MacLeod RA.; 1974 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245817
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Potassium Transport into Plant Vacuoles Energized Directly by a Proton-Pumping Inorganic Pyrophosphatase. by Davies JM, Poole RJ, Rea PA, Sanders D.; 1992 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50624
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Potassium transport system of Rhodopseudomonas capsulata. by Jasper P.; 1978 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222168
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Potassium/proton antiport system of growing Enterococcus hirae at high pH. by Kakinuma Y, Igarashi K.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176872
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Potassium-Channel Activation in Response to Low Doses of [gamma]-Irradiation Involves Reactive Oxygen Intermediates in Nonexcitatory Cells. by Kuo SS, Saad AH, Koong AC, Hahn GM, Giaccia AJ.; 1993 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45779
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Potassium-resistant triple helix formation and improved intracellular gene targeting by oligodeoxyribonucleotides containing 7-deazaxanthine. by Faruqi AF, Krawczyk SH, Matteucci MD, Glazer PM.; 1997 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146453
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Primary Structure and Functional Expression of a cGMP-Gated Potassium Channel. by Yao X, Segal AS, Welling P, Zhang X, McNicholas CM, Engel D, Boulpaep EL, Desir GV.; 1995 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40472
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Protein Synthesis in Bacillus subtilis: Differential Effect of Potassium Ions on In Vitro Peptide Chain Initiation and Elongation. by Sala F, Bazzicalupo M, Parisi B.; 1974 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245686
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Pyridine Nucleotide Redox State Parallels Production of Aldosterone in PotassiumStimulated Adrenal Glomerulosa Cells. by Pralong W, Hunyady L, Varnai P, Wollheim CB, Spat A.; 1992 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48190
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Rapid Induction of Regulatory and Transporter Genes in Response to Phosphorus, Potassium, and Iron Deficiencies in Tomato Roots. Evidence for Cross Talk and Root/Rhizosphere-Mediated Signals. by Wang YH, Garvin DF, Kochian LV.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166655
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Rapid Up-Regulation of HKT1, a High-Affinity Potassium Transporter Gene, in Roots of Barley and Wheat following Withdrawal of Potassium. by Wang TB, Gassmann W, Rubio F, Schroeder JI, Glass AD.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34841
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Regulation of Arabidopsis thaliana (L.) Heynh Arginine decarboxylase by potassium deficiency stress. by Watson MB, Malmberg RL.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=160983
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Regulation of Potassium-Dependent Kdp-ATPase Expression in the Nitrogen-Fixing Cyanobacterium Anabaena torulosa. by Alahari A, Ballal A, Apte SK.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95474
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Role of Sodium and Potassium Ions in Regulation of Glucose Metabolism in Cultured Astroglia. by Takahashi S, Driscoll BF, Law MJ, Sokoloff L.; 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41995
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Selective Knockout of Mouse ERG1 B Potassium Channel Eliminates IKr in Adult Ventricular Myocytes and Elicits Episodes of Abrupt Sinus Bradycardia. by LeesMiller JP, Guo J, Somers JR, Roach DE, Sheldon RS, Rancourt DE, Duff HJ.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149456
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Structures of the potassium-saturated, 2:1, and intermediate, 1:1, forms of a quadruplex DNA. by Marathias VM, Bolton PH.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103305
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Subcloning, nucleotide sequence, and expression of trkG, a gene that encodes an integral membrane protein involved in potassium uptake via the Trk system of Escherichia coli. by Schlosser A, Kluttig S, Hamann A, Bakker EP.; 1991 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207911
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Survival during exposure to the electrophilic reagent N-ethylmaleimide in Escherichia coli: role of KefB and KefC potassium channels. by Ferguson GP, Nikolaev Y, McLaggan D, Maclean M, Booth IR.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178791
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Tetracycline resistance element of pBR322 mediates potassium transport. by Dosch DC, Salvacion FF, Epstein W.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215843
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The Amino-Terminal Segment of the Catalytic Subunit of Kidney Na,K-ATPase Regulates the Potassium Deocclusion Pathway of the Reaction Cycle. by Wierzbicki W, Blostein R.; 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45601
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The effect of sodium, potassium and ammonium ions on the conformation of the dimeric quadruplex formed by the Oxytricha nova telomere repeat oligonucleotide d(G(4)T(4)G(4)). by Schultze P, Hud NV, Smith FW, Feigon J.; 1999 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148525
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The HAK1 gene of barley is a member of a large gene family and encodes a highaffinity potassium transporter. by Santa-Maria GE, Rubio F, Dubcovsky J, RodriguezNavarro A.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157074
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The kdp system of Clostridium acetobutylicum: cloning, sequencing, and transcriptional regulation in response to potassium concentration. by Treuner-Lange A, Kuhn A, Durre P.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179285
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The tet(K) gene from Staphylococcus aureus mediates the transport of potassium in Escherichia coli. by Guay GG, Tuckman M, McNicholas P, Rothstein DM.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204949
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TRH1 Encodes a Potassium Transporter Required for Tip Growth in Arabidopsis Root Hairs. by Rigas S, Debrosses G, Haralampidis K, Vicente-Agullo F, Feldmann KA, Grabov A, Dolan L, Hatzopoulos P.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102205
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Use of potassium depletion to assess adaptation of ruminal bacteria to ionophores. by Lana RP, Russell JB.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168276
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with potassium, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “potassium” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for potassium (hyperlinks lead to article summaries): •
A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels. Author(s): Gu C, Jan YN, Jan LY. Source: Science. 2003 August 1; 301(5633): 646-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893943&dopt=Abstract
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A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. Author(s): Dias Da Silva MR, Cerutti JM, Arnaldi LA, Maciel RM. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 4881-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414843&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A new human gene KCNRG encoding potassium channel regulating protein is a cancer suppressor gene candidate located in 13q14.3. Author(s): Ivanov DV, Tyazhelova TV, Lemonnier L, Kononenko N, Pestova AA, Nikitin EA, Prevarskaya N, Skryma R, Panchin YV, Yankovsky NK, Baranova AV. Source: Febs Letters. 2003 March 27; 539(1-3): 156-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650944&dopt=Abstract
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A novel conotoxin inhibiting vertebrate voltage-sensitive potassium channels. Author(s): Kauferstein S, Huys I, Lamthanh H, Stocklin R, Sotto F, Menez A, Tytgat J, Mebs D. Source: Toxicon : Official Journal of the International Society on Toxinology. 2003 July; 42(1): 43-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893060&dopt=Abstract
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A novel mutation (T65P) in the PAS domain of the human potassium channel HERG results in the long QT syndrome by trafficking deficiency. Author(s): Paulussen A, Raes A, Matthijs G, Snyders DJ, Cohen N, Aerssens J. Source: The Journal of Biological Chemistry. 2002 December 13; 277(50): 48610-6. Epub 2002 September 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354768&dopt=Abstract
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A novel potassium sensing in aqueous media with a synthetic oligonucleotide derivative. Fluorescence resonance energy transfer associated with Guanine quartetpotassium ion complex formation. Author(s): Ueyama H, Takagi M, Takenaka S. Source: Journal of the American Chemical Society. 2002 December 4; 124(48): 14286-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452685&dopt=Abstract
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A patient with sodium- and potassium-losing nephropathy. Author(s): Fulop M. Source: The American Journal of the Medical Sciences. 2003 February; 325(2): 93-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589233&dopt=Abstract
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A potassium ion channel is involved in cytokine production by activated human macrophages. Author(s): Qiu MR, Campbell TJ, Breit SN. Source: Clinical and Experimental Immunology. 2002 October; 130(1): 67-74. Erratum In: Clin Exp Immunol 2002 December; 130(3): 559-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296855&dopt=Abstract
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A trail of research on potassium. Author(s): Giebisch GH. Source: Kidney International. 2002 November; 62(5): 1498-512. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371944&dopt=Abstract
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Ace inhibitors and survival in dialysis patients: effects on serum potassium? Author(s): Abbott KC. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 February; 41(2): 520-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552520&dopt=Abstract
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Active relaxation of human gallbladder muscle is mediated by ATP-sensitive potassium channels. Author(s): Bird NC, Ahmed R, Chess-Williams R, Johnson AG. Source: Digestion. 2002; 65(4): 220-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239463&dopt=Abstract
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Activity of potassium channel-blockers in breast cancer. Author(s): Abdul M, Santo A, Hoosein N. Source: Anticancer Res. 2003 July-August; 23(4): 3347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926074&dopt=Abstract
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Airway obstruction following potassium permanganate ingestion. Author(s): Dhamrait RS. Source: Anaesthesia. 2003 June; 58(6): 606-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846640&dopt=Abstract
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Analysis of phosphorylation-dependent modulation of Kv1.1 potassium channels. Author(s): Winklhofer M, Matthias K, Seifert G, Stocker M, Sewing S, Herget T, Steinhauser C, Saaler-Reinhardt S. Source: Neuropharmacology. 2003 May; 44(6): 829-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681381&dopt=Abstract
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APETx1, a new toxin from the sea anemone Anthopleura elegantissima, blocks voltage-gated human ether-a-go-go-related gene potassium channels. Author(s): Diochot S, Loret E, Bruhn T, Beress L, Lazdunski M. Source: Molecular Pharmacology. 2003 July; 64(1): 59-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815161&dopt=Abstract
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ATP-sensitive potassium channels in the cerebral circulation. Author(s): Rosenblum WI. Source: Stroke; a Journal of Cerebral Circulation. 2003 June; 34(6): 1547-52. Epub 2003 April 24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714709&dopt=Abstract
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ATP-sensitive potassium channels induced in liver cells after transfection with insulin cDNA and the GLUT 2 transporter regulate glucose-stimulated insulin secretion. Author(s): Liu GJ, Simpson AM, Swan MA, Tao C, Tuch BE, Crawford RM, Jovanovic A, Martin DK. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 September; 17(12): 1682-4. Epub 2003 July 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958175&dopt=Abstract
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A-type potassium currents in smooth muscle. Author(s): Amberg GC, Koh SD, Imaizumi Y, Ohya S, Sanders KM. Source: American Journal of Physiology. Cell Physiology. 2003 March; 284(3): C583-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556357&dopt=Abstract
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Autoimmune disorders of neuronal potassium channels. Author(s): Newsom-Davis J, Buckley C, Clover L, Hart I, Maddison P, Tuzum E, Vincent A. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 202-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592877&dopt=Abstract
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Banana potassium and stroke. Author(s): Singhal MK. Source: Indian J Exp Biol. 2002 November; 40(11): 1322. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677640&dopt=Abstract
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Bcl-2 and tBid proteins counter-regulate mitochondrial potassium transport. Author(s): Eliseev RA, Salter JD, Gunter KK, Gunter TE. Source: Biochimica Et Biophysica Acta. 2003 April 18; 1604(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686415&dopt=Abstract
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Beneficial effect of glucose-insulin-potassium infusion in noncritically ill patients has to be proven. Author(s): van der Horst IC, Gans RO, Nijsten MW, Ligtenberg JJ. Source: Journal of Internal Medicine. 2003 November; 254(5): 513; Author Reply 514. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535974&dopt=Abstract
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Beta-oxidation of 5-hydroxydecanoate, a putative blocker of mitochondrial ATPsensitive potassium channels. Author(s): Hanley PJ, Gopalan KV, Lareau RA, Srivastava DK, von Meltzer M, Daut J. Source: The Journal of Physiology. 2003 March 1; 547(Pt 2): 387-93. Epub 2003 January 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562916&dopt=Abstract
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Bioequivalence of clavulanate potassium and amoxicillin (1:7) dispersible tablets in healthy volunteers. Author(s): Hu G, Dai Z, Long L, Han Y, Hou S, Wu L. Source: J Huazhong Univ Sci Technolog Med Sci. 2002; 22(3): 224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658810&dopt=Abstract
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Biophysical characteristics of a new mutation on the KCNQ1 potassium channel (L251P) causing long QT syndrome. Author(s): Deschenes D, Acharfi S, Pouliot V, Hegele R, Krahn A, Daleau P, Chahine M. Source: Canadian Journal of Physiology and Pharmacology. 2003 February; 81(2): 12934. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710526&dopt=Abstract
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Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. Author(s): Geleijnse JM, Kok FJ, Grobbee DE. Source: Journal of Human Hypertension. 2003 July; 17(7): 471-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821954&dopt=Abstract
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BMS-204352: a potassium channel opener developed for the treatment of stroke. Author(s): Jensen BS. Source: Cns Drug Rev. 2002 Winter; 8(4): 353-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481191&dopt=Abstract
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BPDZ 154 activates adenosine 5'-triphosphate-sensitive potassium channels: in vitro studies using rodent insulin-secreting cells and islets isolated from patients with hyperinsulinism. Author(s): Cosgrove KE, Antoine MH, Lee AT, Barnes PD, de Tullio P, Clayton P, McCloy R, De Lonlay P, Nihoul-Fekete C, Robert JJ, Saudubray JM, Rahier J, Lindley KJ, Hussain K, Aynsley-Green A, Pirotte B, Lebrun P, Dunne MJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 November; 87(11): 4860-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414839&dopt=Abstract
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By the way, doctor. I'm 84, 5-foot-9, and weigh 160. I do an hour's exercise every day. I take a diuretic, potassium, and calcium-channel blocker. Should I also take Lipitor to avoid a heart attack? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2003 April; 28(6): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777236&dopt=Abstract
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Calcium activation of BK(Ca) potassium channels lacking the calcium bowl and RCK domains. Author(s): Piskorowski R, Aldrich RW. Source: Nature. 2002 December 5; 420(6915): 499-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466841&dopt=Abstract
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Calcium-activated potassium channel expression in human myometrium: effect of pregnancy. Author(s): Mazzone JN, Kaiser RA, Buxton IL. Source: Proc West Pharmacol Soc. 2002; 45: 184-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434576&dopt=Abstract
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Capping carious exposed pulps with potassium nitrate, dimethyl isosorbide, polycarboxylate cement. Author(s): Hodosh M, Hodosh SH, Hodosh AJ. Source: Dent Today. 2003 January; 22(1): 46-51. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12616888&dopt=Abstract
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Cardiac sympathetic innervation and control of potassium channel function. Author(s): Ravens U, Dobrev D. Source: Journal of Molecular and Cellular Cardiology. 2003 February; 35(2): 137-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606253&dopt=Abstract
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Caustic burn caused by potassium permanganate. Author(s): Baron S, Moss C. Source: Archives of Disease in Childhood. 2003 February; 88(2): 96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538301&dopt=Abstract
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Ceramide inhibits the potassium channel Kv1.3 by the formation of membrane platforms. Author(s): Bock J, Szabo I, Gamper N, Adams C, Gulbins E. Source: Biochemical and Biophysical Research Communications. 2003 June 13; 305(4): 890-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767914&dopt=Abstract
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Chloride and potassium channel function in alveolar epithelial cells. Author(s): O'Grady SM, Lee SY. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 May; 284(5): L689-700. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676759&dopt=Abstract
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Chronic treatment with nicotine or potassium attenuates depolarisation-evoked noradrenaline release from the human neuroblastoma SH-SY5Y. Author(s): Agis-Torres A, Ball SG, Vaughan PF. Source: Neuroscience Letters. 2002 October 18; 331(3): 167-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383923&dopt=Abstract
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Cloning of a pore-forming subunit of ATP-sensitive potassium channel from Clonorchis sinensis. Author(s): Hwang SY, Han HJ, Kim SH, Park SG, Seog DH, Kim NR, Han J, Chung JY, Kho WG. Source: The Korean Journal of Parasitology. 2003 June; 41(2): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12815327&dopt=Abstract
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Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes. Author(s): Panyi G, Bagdany M, Bodnar A, Vamosi G, Szentesi G, Jenei A, Matyus L, Varga S, Waldmann TA, Gaspar R, Damjanovich S. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 4; 100(5): 2592-7. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604782&dopt=Abstract
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Comparative response of whitening strips to a low peroxide and potassium nitrate bleaching gel. Author(s): Gerlach RW, Zhou X, McClanahan SF. Source: Am J Dent. 2002 September; 15 Spec No: 19A-23A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512987&dopt=Abstract
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Contribution of nitric oxide to potassium bromate-induced elevation of methaemoglobin concentration in mouse blood. Author(s): Watanabe S, Togashi S, Fukui T. Source: Biological & Pharmaceutical Bulletin. 2002 October; 25(10): 1315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392086&dopt=Abstract
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Control of outer vestibule dynamics and current magnitude in the Kv2.1 potassium channel. Author(s): Andalib P, Wood MJ, Korn SJ. Source: The Journal of General Physiology. 2002 November; 120(5): 739-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407083&dopt=Abstract
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Correction for the adverse influence of sodium-potassium cotransport on apparent sodium-lithium countertransport activity in human erythrocytes. Author(s): Hardman TC, Morrish Z, Patel M, Chalkley S, Noble MI. Source: Journal of Pharmacological and Toxicological Methods. 2002 January-February; 47(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387935&dopt=Abstract
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Cranial MR imaging findings of potassium chlorate intoxication. Author(s): Mutlu H, Silit E, Pekkafali Z, Basekim CC, Kizilkaya E, Ay H, Karsli AF. Source: Ajnr. American Journal of Neuroradiology. 2003 August; 24(7): 1396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917136&dopt=Abstract
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C-terminal domains implicated in the functional surface expression of potassium channels. Author(s): Jenke M, Sanchez A, Monje F, Stuhmer W, Weseloh RM, Pardo LA. Source: The Embo Journal. 2003 February 3; 22(3): 395-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554641&dopt=Abstract
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Danger of salt substitutes that contain potassium in patients with renal failure. Author(s): Doorenbos CJ, Vermeij CG. Source: Bmj (Clinical Research Ed.). 2003 January 4; 326(7379): 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511461&dopt=Abstract
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Decreased potassium channel IK1 and its regulator neurotrophin-3 (NT-3) in inflamed human bowel. Author(s): Arnold SJ, Facer P, Yiangou Y, Chen MX, Plumpton C, Tate SN, Bountra C, Chan CL, Williams NS, Anand P. Source: Neuroreport. 2003 February 10; 14(2): 191-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598727&dopt=Abstract
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Detection and implications of potassium channel alterations. Author(s): Korovkina VP, England SK. Source: Vascular Pharmacology. 2002 January; 38(1): 3-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378820&dopt=Abstract
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Diabetes mellitus impairs vasodilation to hypoxia in human coronary arterioles: reduced activity of ATP-sensitive potassium channels. Author(s): Miura H, Wachtel RE, Loberiza FR Jr, Saito T, Miura M, Nicolosi AC, Gutterman DD. Source: Circulation Research. 2003 February 7; 92(2): 151-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574142&dopt=Abstract
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Diazoxide in the treatment of schizophrenia: novel application of potassium channel openers in the treatment of schizophrenia. Author(s): Akhondzadeh S, Mojtahedzadeh V, Mirsepassi GR, Moin M, AminiNooshabadi H, Kamalipour A. Source: Journal of Clinical Pharmacy and Therapeutics. 2002 December; 27(6): 453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472985&dopt=Abstract
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Dietary potassium and laxatives as regulators of colonic potassium secretion in endstage renal disease. Author(s): Mathialahan T, Sandle GI. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 February; 18(2): 341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543890&dopt=Abstract
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Dietary protein, phosphorus and potassium are beneficial to bone mineral density in adult men consuming adequate dietary calcium. Author(s): Whiting SJ, Boyle JL, Thompson A, Mirwald RL, Faulkner RA. Source: Journal of the American College of Nutrition. 2002 October; 21(5): 402-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356781&dopt=Abstract
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Distal nephron sodium-potassium exchange in children with nephrotic syndrome. Author(s): Donckerwolcke RA, France A, Raes A, Vande Walle J. Source: Clinical Nephrology. 2003 April; 59(4): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708565&dopt=Abstract
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E23K single nucleotide polymorphism in the islet ATP-sensitive potassium channel gene (Kir6.2) contributes as much to the risk of Type II diabetes in Caucasians as the PPARgamma Pro12Ala variant. Author(s): Love-Gregory L, Wasson J, Lin J, Skolnick G, Suarez B, Permutt MA. Source: Diabetologia. 2003 January; 46(1): 136-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643262&dopt=Abstract
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Effect of chronic tobacco use on salivary concentrations of sodium and potassium. Author(s): Khan GJ, Mehmood R, Salah-ud-Din, Ihtesham-ul-Haq. Source: J Ayub Med Coll Abbottabad. 2003 January-March; 15(1): 41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870317&dopt=Abstract
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Effect of diabetes on serum potassium concentrations in acute coronary syndromes. Author(s): Foo K, Sekhri N, Deaner A, Knight C, Suliman A, Ranjadayalan K, Timmis AD. Source: Heart (British Cardiac Society). 2003 January; 89(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482786&dopt=Abstract
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Effect of different cycling frequencies during incremental exercise on the venous plasma potassium concentration in humans. Author(s): Zoladz JA, Duda K, Majerczak J, Thor P. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2002; 51(6): 581-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511181&dopt=Abstract
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Effect of lipophylic salts on ise detection limit: application to calixarene-based highly efficient potassium-selective electrodes. Author(s): Giannetto M, Mori G, Pappalardo S, Parisi MF. Source: Ann Chim. 2002 November-December; 92(11-12): 1099-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556033&dopt=Abstract
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Effect of low-molecular-weight heparin on potassium homeostasis. Author(s): Abdel-Raheem MM, Potti A, Tadros S, Koka V, Hanekom D, Fraiman G, Danielson BD. Source: Pathophysiology of Haemostasis and Thrombosis. 2002 May-June; 32(3): 107-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372922&dopt=Abstract
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Effect of S6 tail mutations on charge movement in Shaker potassium channels. Author(s): Ding S, Horn R. Source: Biophysical Journal. 2003 January; 84(1): 295-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524283&dopt=Abstract
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Effects of a potassium nitrate mouthwash on dentinal tubules--a SEM analysis using the dentine disc model. Author(s): Pereira R, Chava VK. Source: J Int Acad Periodontol. 2002 April; 4(2): 44-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685807&dopt=Abstract
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Effects of adrenaline and potassium on QTc interval and QT dispersion in man. Author(s): Lee S, Harris ND, Robinson RT, Yeoh L, Macdonald IA, Heller SR. Source: European Journal of Clinical Investigation. 2003 February; 33(2): 93-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588281&dopt=Abstract
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Effects of glucose-insulin-potassium infusion on chronic ischaemic left ventricular dysfunction. Author(s): Khoury VK, Haluska B, Prins J, Marwick TH. Source: Heart (British Cardiac Society). 2003 January; 89(1): 61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482794&dopt=Abstract
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Effects of glucose-insulin-potassium solution on myocardial salvage and left ventricular function after primary angioplasty. Author(s): Castro PF, Larrain G, Baeza R, Corbalan R, Nazzal C, Greig DP, Miranda FP, Perez O, Acevedo M, Marchant E, Olea E, Gonzalez R. Source: Critical Care Medicine. 2003 August; 31(8): 2152-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12973173&dopt=Abstract
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Effects of inhibition of ATP-sensitive potassium channels on metabolic vasodilation in the human forearm. Author(s): Farouque HM, Meredith IT. Source: Clinical Science (London, England : 1979). 2003 January; 104(1): 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12519086&dopt=Abstract
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Effects of irbesartan on cloned potassium channels involved in human cardiac repolarization. Author(s): Moreno I, Caballero R, Gonzalez T, Arias C, Valenzuela C, Iriepa I, Galvez E, Tamargo J, Delpon E. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 February; 304(2): 862-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538844&dopt=Abstract
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Effects of sulfonylurea hypoglycemic agents and adenosine triphosphate dependent potassium channel antagonists on ventricular arrhythmias in patients with decompensated heart failure. Author(s): Aronson D, Mittleman MA, Burger AJ. Source: Pacing and Clinical Electrophysiology : Pace. 2003 May; 26(5): 1254-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765455&dopt=Abstract
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Elevated non-esterified fatty acids impair nitric oxide independent vasodilation, in humans: evidence for a role of inwardly rectifying potassium channels. Author(s): de Kreutzenberg SV, Puato M, Kiwanuka E, Del Prato S, Pauletto P, Pasini L, Tiengo A, Avogaro A. Source: Atherosclerosis. 2003 July; 169(1): 147-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860261&dopt=Abstract
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Engineering-specific pharmacological binding sites for peptidyl inhibitors of potassium channels into KcsA. Author(s): Legros C, Schulze C, Garcia ML, Bougis PE, Martin-Eauclaire MF, Pongs O. Source: Biochemistry. 2002 December 24; 41(51): 15369-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12484776&dopt=Abstract
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Esophageal hemangioma successfully treated by fulguration using potassium titanyl phosphate/yttrium aluminum garnet (KTP/YAG) laser: a case report. Author(s): Shigemitsu K, Naomoto Y, Yamatsuji T, Ono K, Aoki H, Haisa M, Tanaka N. Source: Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus / I.S.D.E. 2000; 13(2): 161-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14601909&dopt=Abstract
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Estrogen and adenosine triphosphate-sensitive potassium channels. Author(s): Webb C, Collins P. Source: Circulation. 2003 June 24; 107(24): E221; Author Reply E221. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821597&dopt=Abstract
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Evaluation of the efficacy of two potassium nitrate bioadhesive gels (5% and 10%) in the treatment of dentine hypersensitivity. A randomised clinical trial. Author(s): Frechoso SC, Menendez M, Guisasola C, Arregui I, Tejerina JM, Sicilia A. Source: Journal of Clinical Periodontology. 2003 April; 30(4): 315-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694429&dopt=Abstract
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Experimental and theoretical studies of the effect of electrode polarisation on capacitances of blood and potassium chloride solution. Author(s): Umino M, Oda N, Yasuhara Y. Source: Medical & Biological Engineering & Computing. 2002 September; 40(5): 533-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452413&dopt=Abstract
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Experts advise on potassium iodide use: no protection against “dirty bombs”. Author(s): Vastag B. Source: Jama : the Journal of the American Medical Association. 2003 April 23-30; 289(16): 2058. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709449&dopt=Abstract
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Expression and distribution of a small-conductance calcium-activated potassium channel (SK3) protein in skeletal muscles from myotonic muscular dystrophy patients and congenital myotonic mice. Author(s): Kimura T, Takahashi MP, Fujimura H, Sakoda S. Source: Neuroscience Letters. 2003 August 28; 347(3): 191-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875918&dopt=Abstract
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Expression of mRNA transcripts for ATP-sensitive potassium channels in human myometrium. Author(s): Curley M, Cairns MT, Friel AM, McMeel OM, Morrison JJ, Smith TJ. Source: Molecular Human Reproduction. 2002 October; 8(10): 941-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356945&dopt=Abstract
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Expression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas. Author(s): Preussat K, Beetz C, Schrey M, Kraft R, Wolfl S, Kalff R, Patt S. Source: Neuroscience Letters. 2003 July 31; 346(1-2): 33-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850541&dopt=Abstract
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Fatal intravenous injection of potassium in hospitalized patients. Author(s): Wetherton AR, Corey TS, Buchino JJ, Burrows AM. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2003 June; 24(2): 128-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773847&dopt=Abstract
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Final report on the safety assessment of Tocopherol, Tocopheryl Acetate, Tocopheryl Linoleate, Tocopheryl Linoleate/Oleate, Tocopheryl Nicotinate, Tocopheryl Succinate, Dioleyl Tocopheryl Methylsilanol, Potassium Ascorbyl Tocopheryl Phosphate, and Tocophersolan. Author(s): Zondlo Fiume M. Source: International Journal of Toxicology. 2002; 21 Suppl 3: 51-116. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537931&dopt=Abstract
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Functional and pharmacological properties of canine ERG potassium channels. Author(s): Wang J, Della Penna K, Wang H, Karczewski J, Connolly TM, Koblan KS, Bennett PB, Salata JJ. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2003 January; 284(1): H256-67. Epub 2002 October 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388285&dopt=Abstract
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G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase. Author(s): Lavine N, Ethier N, Oak JN, Pei L, Liu F, Trieu P, Rebois RV, Bouvier M, Hebert TE, Van Tol HH. Source: The Journal of Biological Chemistry. 2002 November 29; 277(48): 46010-9. Epub 2002 September 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297500&dopt=Abstract
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Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. Author(s): Mu D, Chen L, Zhang X, See LH, Koch CM, Yen C, Tong JJ, Spiegel L, Nguyen KC, Servoss A, Peng Y, Pei L, Marks JR, Lowe S, Hoey T, Jan LY, McCombie WR, Wigler MH, Powers S. Source: Cancer Cell. 2003 March; 3(3): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676587&dopt=Abstract
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Glucose-insulin-potassium infusion in sepsis and septic shock: no hard evidence yet. Author(s): van der Horst IC, Ligtenberg JJ, Bilo HJ, Zijlstra F, Gans RO. Source: Critical Care (London, England). 2003 February; 7(1): 13-5. Epub 2002 October 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617733&dopt=Abstract
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Glucose-insulin-potassium infusion inpatients treated with primary angioplasty for acute myocardial infarction: the glucose-insulin-potassium study: a randomized trial. Author(s): van der Horst IC, Zijlstra F, van't Hof AW, Doggen CJ, de Boer MJ, Suryapranata H, Hoorntje JC, Dambrink JH, Gans RO, Bilo HJ; Zwolle Infarct Study Group. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 784-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957421&dopt=Abstract
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Growth differentiation factor-15 prevents low potassium-induced cell death of cerebellar granule neurons by differential regulation of Akt and ERK pathways. Author(s): Subramaniam S, Strelau J, Unsicker K. Source: The Journal of Biological Chemistry. 2003 March 14; 278(11): 8904-12. Epub 2003 January 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514175&dopt=Abstract
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High potassium-induced activation of choline-acetyltransferase in human neocortex: implications and species differences. Author(s): Sigle JP, Zander J, Ehret A, Honegger J, Jackisch R, Feuerstein TJ. Source: Brain Research Bulletin. 2003 May 15; 60(3): 255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754087&dopt=Abstract
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High salt intake appears to increase bone resorption in postmenopausal women but high potassium intake ameliorates this adverse effect. Author(s): Harrington M, Cashman KD. Source: Nutrition Reviews. 2003 May; 61(5 Pt 1): 179-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822707&dopt=Abstract
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High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues. Author(s): Szabo Z, Hakanson E, Maros T, Svedjeholm R. Source: Acta Anaesthesiologica Scandinavica. 2003 April; 47(4): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694134&dopt=Abstract
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Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition. Author(s): Hampl V, Bibova J, Stranak Z, Wu X, Michelakis ED, Hashimoto K, Archer SL. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2002 December; 283(6): H2440-9. Epub 2002 August 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388256&dopt=Abstract
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Identification of a COOH-terminal segment involved in maturation and stability of human ether-a-go-go-related gene potassium channels. Author(s): Akhavan A, Atanasiu R, Shrier A. Source: The Journal of Biological Chemistry. 2003 October 10; 278(41): 40105-12. Epub 2003 July 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885765&dopt=Abstract
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Identification of human Kir2.2 (KCNJ12) gene encoding functional inward rectifier potassium channel in both mammalian cells and Xenopus oocytes. Author(s): Kaibara M, Ishihara K, Doi Y, Hayashi H, Ehara T, Taniyama K. Source: Febs Letters. 2002 November 6; 531(2): 250-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417321&dopt=Abstract
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Identification of viable myocardium in patients with chronic coronary artery disease and myocardial dysfunction: comparison of low-dose dobutamine stress echocardiography and echocardiography during glucose-insulin-potassium infusion. Author(s): Yetkin E, Senen K, Ileri M, Atak R, Battaoglu B, Yetkin O, Tandogan I, Turhan H, Cehreli S. Source: Angiology. 2002 November-December; 53(6): 671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463620&dopt=Abstract
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Identification, synthesis, and activity of novel blockers of the voltage-gated potassium channel Kv1.5. Author(s): Peukert S, Brendel J, Pirard B, Bruggemann A, Below P, Kleemann HW, Hemmerle H, Schmidt W. Source: Journal of Medicinal Chemistry. 2003 February 13; 46(4): 486-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570371&dopt=Abstract
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Immunolocalization and protein expression of the alpha subunit of the largeconductance calcium-activated potassium channel in human myometrium. Author(s): Chanrachakul B, Matharoo-Ball B, Turner A, Robinson G, Broughton-Pipkin F, Arulkumaran S, Khan RN. Source: Reproduction (Cambridge, England). 2003 July; 126(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814346&dopt=Abstract
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Impaired hypoxic coronary vasodilation and ATP-sensitive potassium channel function: a manifestation of diabetic microangiopathy in humans? Author(s): Weintraub NL. Source: Circulation Research. 2003 February 7; 92(2): 127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574137&dopt=Abstract
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Inactivation of Kv3.3 potassium channels in heterologous expression systems. Author(s): Fernandez FR, Morales E, Rashid AJ, Dunn RJ, Turner RW. Source: The Journal of Biological Chemistry. 2003 October 17; 278(42): 40890-8. Epub 2003 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923191&dopt=Abstract
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Increased prevalence of interstitial cystitis: previously unrecognized urologic and gynecologic cases identified using a new symptom questionnaire and intravesical potassium sensitivity. Author(s): Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Waxell T, Koziol JA. Source: Urology. 2002 October; 60(4): 573-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385909&dopt=Abstract
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Increasing blood flow increases kt/V(urea) and potassium removal but fails to improve phosphate removal. Author(s): Gutzwiller JP, Schneditz D, Huber AR, Schindler C, Garbani E, Zehnder CE. Source: Clinical Nephrology. 2003 February; 59(2): 130-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608556&dopt=Abstract
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Increasing plasma potassium with amiloride shortens the QT interval and reduces ventricular extrasystoles but does not change endothelial function or heart rate variability in chronic heart failure. Author(s): Farquharson CA, Struthers AD. Source: Heart (British Cardiac Society). 2002 November; 88(5): 475-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381637&dopt=Abstract
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Influence of pore residues on permeation properties in the Kv2.1 potassium channel. Evidence for a selective functional interaction of K+ with the outer vestibule. Author(s): Consiglio JF, Andalib P, Korn SJ. Source: The Journal of General Physiology. 2003 February; 121(2): 111-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566539&dopt=Abstract
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Inhibition of hEAG1 and hERG1 potassium channels by clofilium and its tertiary analogue LY97241. Author(s): Gessner G, Heinemann SH. Source: British Journal of Pharmacology. 2003 January; 138(1): 161-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522086&dopt=Abstract
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Interaction with 14-3-3 proteins promotes functional expression of the potassium channels TASK-1 and TASK-3. Author(s): Rajan S, Preisig-Muller R, Wischmeyer E, Nehring R, Hanley PJ, Renigunta V, Musset B, Schlichthorl G, Derst C, Karschin A, Daut J. Source: The Journal of Physiology. 2002 November 15; 545(Pt 1): 13-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433946&dopt=Abstract
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Intraerythrocytic potassium levels and early insulin release in children with moderate malnutrition. Author(s): Karasalihoglu S, Bi M, Oner N, Celtik C, Pala O. Source: Journal of Tropical Pediatrics. 2003 October; 49(5): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604166&dopt=Abstract
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Inwardly rectifying potassium channels in the regulation of vascular tone. Author(s): Chrissobolis S, Sobey CG. Source: Current Drug Targets. 2003 May; 4(4): 281-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699348&dopt=Abstract
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Iodinated contrast medium-induced potassium release: the effect of mixing ratios. Author(s): Hayakawa K, Nakamura T, Shimizu Y. Source: Radiat Med. 2002 July-August; 20(4): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296436&dopt=Abstract
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Is potassium concentration from arterial blood gas analysis an accurate reflection of serum potassium? Author(s): Kelly AM, Middleton P. Source: Emergency Medicine (Fremantle, W.A.). 2003 June; 15(3): 301-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786659&dopt=Abstract
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Keratosis rubra pilaris responding to potassium titanyl phosphate laser. Author(s): Dawn G, Urcelay M, Patel M, Strong AM. Source: The British Journal of Dermatology. 2002 October; 147(4): 822-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366447&dopt=Abstract
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Killing of Candida albicans by human salivary histatin 5 is modulated, but not determined, by the potassium channel TOK1. Author(s): Baev D, Rivetta A, Li XS, Vylkova S, Bashi E, Slayman CL, Edgerton M. Source: Infection and Immunity. 2003 June; 71(6): 3251-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761106&dopt=Abstract
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Kinetic modulation of HERG potassium channels by the volatile anesthetic halothane. Author(s): Li J, Correa AM. Source: Anesthesiology. 2002 October; 97(4): 921-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357160&dopt=Abstract
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Kir6.2 polymorphisms sensitize beta-cell ATP-sensitive potassium channels to activation by acyl CoAs: a possible cellular mechanism for increased susceptibility to type 2 diabetes? Author(s): Riedel MJ, Boora P, Steckley D, de Vries G, Light PE. Source: Diabetes. 2003 October; 52(10): 2630-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514649&dopt=Abstract
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KTP laser ablation of Barrett's esophagus after anti-reflux surgery results in long-term loss of intestinal metaplasia. Potassium-titanyl-phosphate. Author(s): Bowers SP, Mattar SG, Waring PJ, Galloway K, Nasir A, Pascal R, Hunter JG, Mattear SG. Source: Surgical Endoscopy. 2003 January; 17(1): 49-54. Epub 2002 October 08. Erratum In: Surg Endosc. 2003 Jan; 17(1): 173. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364985&dopt=Abstract
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Kv1.3 potassium channels in human alveolar macrophages. Author(s): Mackenzie AB, Chirakkal H, North RA. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 October; 285(4): L862-8. Epub 2003 August 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909584&dopt=Abstract
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Levalbuterol is as effective as racemic albuterol in lowering serum potassium. Author(s): Pancu D, LaFlamme M, Evans E, Reed J. Source: The Journal of Emergency Medicine. 2003 July; 25(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865102&dopt=Abstract
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Linearization of the relationship between serum sodium, potassium concentration, their ratio and time since death in Chandigarh zone of north-west India. Author(s): Singh D, Prashad R, Parkash C, Bansal YS, Sharma SK, Pandey AN. Source: Forensic Science International. 2002 November 5; 130(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427443&dopt=Abstract
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Localization and function of ATP-sensitive potassium channels in human skeletal muscle. Author(s): Nielsen JJ, Kristensen M, Hellsten Y, Bangsbo J, Juel C. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003 February; 284(2): R558-63. Epub 2002 September 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388475&dopt=Abstract
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Long-term administration of nicorandil abolishes ischemic and pharmacologic preconditioning of the human myocardium: role of mitochondrial adenosine triphosphate-dependent potassium channels. Author(s): Loubani M, Galinanes M. Source: The Journal of Thoracic and Cardiovascular Surgery. 2002 October; 124(4): 750-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324733&dopt=Abstract
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Low-dose diclofenac potassium in the treatment of episodic tension-type headache. Author(s): Kubitzek F, Ziegler G, Gold MS, Liu JM, Ionescu E. Source: European Journal of Pain (London, England). 2003; 7(2): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600797&dopt=Abstract
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Management of a case of uterine scar pregnancy by transabdominal potassium chloride injection. Author(s): Hartung J, Meckies J. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 January; 21(1): 94-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528170&dopt=Abstract
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Maurotoxin: a potent inhibitor of intermediate conductance Ca2+-activated potassium channels. Author(s): Castle NA, London DO, Creech C, Fajloun Z, Stocker JW, Sabatier JM. Source: Molecular Pharmacology. 2003 February; 63(2): 409-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527813&dopt=Abstract
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Mechanism of inhibitory actions of oxidizing agents on calcium-activated potassium current in cultured pigment epithelial cells of the human retina. Author(s): Sheu SJ, Wu SN. Source: Investigative Ophthalmology & Visual Science. 2003 March; 44(3): 1237-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601054&dopt=Abstract
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MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain. Author(s): McCrossan ZA, Lewis A, Panaghie G, Jordan PN, Christini DJ, Lerner DJ, Abbott GW. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 September 3; 23(22): 8077-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954870&dopt=Abstract
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Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. Author(s): Mattson MP, Liu D. Source: Biochemical and Biophysical Research Communications. 2003 May 9; 304(3): 539-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729589&dopt=Abstract
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Mitochondrial potassium transport: the K(+) cycle. Author(s): Garlid KD, Paucek P. Source: Biochimica Et Biophysica Acta. 2003 September 30; 1606(1-3): 23-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507425&dopt=Abstract
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Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K(+) channel in cardiac function and cardioprotection. Author(s): Garlid KD, Dos Santos P, Xie ZJ, Costa AD, Paucek P. Source: Biochimica Et Biophysica Acta. 2003 September 30; 1606(1-3): 1-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14507424&dopt=Abstract
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Mix-up between potassium chloride and sodium polystyrene sulfonate. Author(s): Kaplan M, Summerfield MR, Pestaner JP. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 September 15; 59(18): 1786-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298122&dopt=Abstract
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Modulation of small conductance calcium-activated potassium (SK) channels: a new challenge in medicinal chemistry. Author(s): Liegeois JF, Mercier F, Graulich A, Graulich-Lorge F, Scuvee-Moreau J, Seutin V. Source: Current Medicinal Chemistry. 2003 April; 10(8): 625-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678783&dopt=Abstract
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Molecular cloning of a fourth member of the potassium-dependent sodium-calcium exchanger gene family, NCKX4. Author(s): Li XF, Kraev AS, Lytton J. Source: The Journal of Biological Chemistry. 2002 December 13; 277(50): 48410-7. Epub 2002 October 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379639&dopt=Abstract
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Molecular site of action of the antiarrhythmic drug propafenone at the voltageoperated potassium channel Kv2.1. Author(s): Madeja M, Leicher T, Friederich P, Punke MA, Haverkamp W, Musshoff U, Breithardt G, Speckmann EJ. Source: Molecular Pharmacology. 2003 March; 63(3): 547-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606761&dopt=Abstract
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Monitoring of transtubular potassium gradient in the diuretic management of patients with cirrhosis and ascites. Author(s): Lim YS, Han JS, Kim KA, Yoon JH, Kim CY, Lee HS. Source: Liver. 2002 October; 22(5): 426-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390478&dopt=Abstract
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Muscle interstitial potassium kinetics during intense exhaustive exercise: effect of previous arm exercise. Author(s): Nordsborg N, Mohr M, Pedersen LD, Nielsen JJ, Langberg H, Bangsbo J. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003 July; 285(1): R143-8. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663256&dopt=Abstract
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Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells. Author(s): Bowley KA, Morton MJ, Hunter M, Sandle GI. Source: Gut. 2003 June; 52(6): 854-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740342&dopt=Abstract
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Noninactivating tandem pore domain potassium channels as attractive targets for general anesthetics. Author(s): Johansson JS. Source: Anesthesia and Analgesia. 2003 May; 96(5): 1248-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707114&dopt=Abstract
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N-terminal PDZ-binding domain in Kv1 potassium channels. Author(s): Eldstrom J, Doerksen KW, Steele DF, Fedida D. Source: Febs Letters. 2002 November 20; 531(3): 529-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435606&dopt=Abstract
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Nucleotide sensitivity of pancreatic ATP-sensitive potassium channels and type 2 diabetes. Author(s): Schwanstecher C, Schwanstecher M. Source: Diabetes. 2002 December; 51 Suppl 3: S358-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475775&dopt=Abstract
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Nutritional and radiological impact of dietary potassium on the Pakistani population. Author(s): Akhter P, Ashraf N, Mohammad D, Orfi SD, Ahmad N. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2003 April; 41(4): 531-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615124&dopt=Abstract
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O-phenylphenol and its sodium and potassium salts: a toxicological assessment. Author(s): Bomhard EM, Brendler-Schwaab SY, Freyberger A, Herbold BA, Leser KH, Richter M. Source: Critical Reviews in Toxicology. 2002; 32(6): 551-625. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487365&dopt=Abstract
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Optimization of a tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors: structure-activity relationship related to PDE4 inhibition and human ether-a-go-go related gene potassium channel binding affinity. Author(s): Friesen RW, Ducharme Y, Ball RG, Blouin M, Boulet L, Cote B, Frenette R, Girard M, Guay D, Huang Z, Jones TR, Laliberte F, Lynch JJ, Mancini J, Martins E, Masson P, Muise E, Pon DJ, Siegl PK, Styhler A, Tsou NN, Turner MJ, Young RN, Girard Y. Source: Journal of Medicinal Chemistry. 2003 June 5; 46(12): 2413-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773045&dopt=Abstract
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Oral potassium citrate treatment for idiopathic hypocitruria in children with calcium urolithiasis. Author(s): Tekin A, Tekgul S, Atsu N, Bakkaloglu M, Kendi S. Source: The Journal of Urology. 2002 December; 168(6): 2572-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441986&dopt=Abstract
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Pemirolast potassium 0.1% ophthalmic solution is an effective treatment for allergic conjunctivitis: a pooled analysis of two prospective, randomized, double-masked, placebo-controlled, phase III studies. Author(s): Abelson MB, Berdy GJ, Mundorf T, Amdahl LD, Graves AL; Pemirolast study group. Source: Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics. 2002 October; 18(5): 475-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419098&dopt=Abstract
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PGE2 action in human coronary artery smooth muscle: role of potassium channels and signaling cross-talk. Author(s): Zhu S, Han G, White RE. Source: Journal of Vascular Research. 2002 November-December; 39(6): 477-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566973&dopt=Abstract
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Pharmacological activation of normal and arrhythmia-associated mutant KCNQ1 potassium channels. Author(s): Seebohm G, Pusch M, Chen J, Sanguinetti MC. Source: Circulation Research. 2003 November 14; 93(10): 941-7. Epub 2003 October 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14576198&dopt=Abstract
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Pharmacology of neuronal background potassium channels. Author(s): Lesage F. Source: Neuropharmacology. 2003 January; 44(1): 1-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559116&dopt=Abstract
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Phenytoin and phenobarbital inhibit human HERG potassium channels. Author(s): Danielsson BR, Lansdell K, Patmore L, Tomson T. Source: Epilepsy Research. 2003 June-July; 55(1-2): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948624&dopt=Abstract
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Plants do it differently. A new basis for potassium/sodium selectivity in the pore of an ion channel. Author(s): Hua BG, Mercier RW, Leng Q, Berkowitz GA. Source: Plant Physiology. 2003 July; 132(3): 1353-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857817&dopt=Abstract
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Potassium antimonyl tartrate induces caspase- and reactive oxygen species-dependent apoptosis in lymphoid tumoral cells. Author(s): Lecureur V, Le Thiec A, Le Meur A, Amiot L, Drenou B, Bernard M, Lamy T, Fauchet R, Fardel O. Source: British Journal of Haematology. 2002 December; 119(3): 608-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437633&dopt=Abstract
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Potassium channels and erectile dysfunction. Author(s): Archer SL. Source: Vascular Pharmacology. 2002 January; 38(1): 61-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378824&dopt=Abstract
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Potassium channels as anti-epileptic drug targets. Author(s): Wickenden AD. Source: Neuropharmacology. 2002 December; 43(7): 1055-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504910&dopt=Abstract
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Potassium channels as therapeutic targets for autoimmune disorders. Author(s): Wulff H, Beeton C, Chandy KG. Source: Curr Opin Drug Discov Devel. 2003 September; 6(5): 640-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14579513&dopt=Abstract
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Potassium channels: structures, models, simulations. Author(s): Sansom MS, Shrivastava IH, Bright JN, Tate J, Capener CE, Biggin PC. Source: Biochimica Et Biophysica Acta. 2002 October 11; 1565(2): 294-307. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409202&dopt=Abstract
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Potassium efflux induced by a new lactoferrin-derived peptide mimicking the effect of native human lactoferrin on the bacterial cytoplasmic membrane. Author(s): Viejo-Diaz M, Andres MT, Perez-Gil J, Sanchez M, Fierro JF. Source: Biochemistry. Biokhimiia. 2003 February; 68(2): 217-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693969&dopt=Abstract
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Potassium oxonate modulation of 5-fluorouracil-induced myelotoxicity in murine and human colony forming assays of hematopoietic precursor cells. Author(s): Kouchi Y, Maeda Y, Ohuchida A, Nomura N. Source: Toxicology Letters. 2002 September 5; 135(1-2): 11-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243859&dopt=Abstract
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Potassium per kilogram fat-free mass and total body potassium: predictions from sex, age, and anthropometry. Author(s): Larsson I, Lindroos AK, Peltonen M, Sjostrom L. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 February; 284(2): E416-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12531747&dopt=Abstract
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Potassium permanganate burn due to a dispensing error. Author(s): Henderson J, Anderson WD, Jawad MA. Source: Burns : Journal of the International Society for Burn Injuries. 2003 June; 29(4): 401-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781624&dopt=Abstract
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Potassium-lowering effect of mineralocorticoid therapy in patients undergoing hemodialysis. Author(s): Furuya R, Kumagai H, Sakao T, Maruyama Y, Hishida A. Source: Nephron. 2002; 92(3): 576-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372940&dopt=Abstract
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Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm-1 scorpion toxin. Author(s): Milnes JT, Dempsey CE, Ridley JM, Crociani O, Arcangeli A, Hancox JC, Witchel HJ. Source: Febs Letters. 2003 July 17; 547(1-3): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860380&dopt=Abstract
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Preparation, characterization & anticancer evaluation of potassium N-(p-anisole)alpha-(2-xanthatophenyl)nitrone. Author(s): Khallow KI, Ezzat SS, al-Omari NA. Source: Boll Chim Farm. 2002 November-December; 141(6): 447-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577515&dopt=Abstract
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Pretreatments with a novel pure potassium channel blocker, Nifekalant, were effective in the electrical atrial defibrillation: a report of two cases. Author(s): Sekita G, Sawaki D, Otani Y, Kobayakawa N, Fukushima K, Takeuchi H, Aoyagi T. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2002 December; 16(6): 551-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797359&dopt=Abstract
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Preventive effect of an antiallergic drug, pemirolast potassium, on restenosis after stent placement: quantitative coronary angiography and intravascular ultrasound studies. Author(s): Ohsawa H, Noike H, Kanai M, Hitsumoto T, Aoyagi K, Sakurai T, Sugiyama Y, Yoshinaga K, Kaku M, Matsumoto J, Iizuka T, Shimizu K, Takahashi M, Tomaru T, Sakuragawa H, Tokuhiro K. Source: J Cardiol. 2003 July; 42(1): 13-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892037&dopt=Abstract
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Properties of potassium currents in Purkinje cells of failing human hearts. Author(s): Han W, Zhang L, Schram G, Nattel S. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2002 December; 283(6): H2495-503. Epub 2002 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388306&dopt=Abstract
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Prospective study of potassium-associated acute transfusion events in pediatric intensive care. Author(s): Parshuram CS, Joffe AR. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 January; 4(1): 65-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656546&dopt=Abstract
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Red blood cell potassium and blood pressure in adolescents: a mixture analysis. Author(s): Delgado MC, Delgado-Almeida A. Source: Nutr Metab Cardiovasc Dis. 2002 June; 12(3): 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12325467&dopt=Abstract
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Redox-sensitive extracellular gates formed by auxiliary beta subunits of calciumactivated potassium channels. Author(s): Zeng XH, Xia XM, Lingle CJ. Source: Nature Structural Biology. 2003 June; 10(6): 448-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740608&dopt=Abstract
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Regulation and critical role of potassium homeostasis in apoptosis. Author(s): Yu SP. Source: Progress in Neurobiology. 2003 July; 70(4): 363-86. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963093&dopt=Abstract
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Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (I(to)). Author(s): Sah R, Ramirez RJ, Oudit GY, Gidrewicz D, Trivieri MG, Zobel C, Backx PH. Source: The Journal of Physiology. 2003 January 1; 546(Pt 1): 5-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509475&dopt=Abstract
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Regulation of cardiac inwardly rectifying potassium channels by membrane lipid metabolism. Author(s): Takano M, Kuratomi S. Source: Progress in Biophysics and Molecular Biology. 2003 January; 81(1): 67-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475570&dopt=Abstract
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Regulation of HERG potassium channel activation by protein kinase C independent of direct phosphorylation of the channel protein. Author(s): Thomas D, Zhang W, Wu K, Wimmer AB, Gut B, Wendt-Nordahl G, Kathofer S, Kreye VA, Katus HA, Schoels W, Kiehn J, Karle CA. Source: Cardiovascular Research. 2003 July 1; 59(1): 14-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829172&dopt=Abstract
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Regulation of mastoparan-induced increase of paracellular permeability in T84 cells by RhoA and basolateral potassium channels. Author(s): Blumenstein I, Gerhard R, Ries J, Kottra G, Stein J. Source: Biochemical Pharmacology. 2003 April 1; 65(7): 1151-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663050&dopt=Abstract
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Relationship of urinary sodium/potassium excretion and calcium intake to blood pressure and prevalence of hypertension among older Chinese vegetarians. Author(s): Kwok TC, Chan TY, Woo J. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571663&dopt=Abstract
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Role of the cytosolic chaperones Hsp70 and Hsp90 in maturation of the cardiac potassium channel HERG. Author(s): Ficker E, Dennis AT, Wang L, Brown AM. Source: Circulation Research. 2003 June 27; 92(12): E87-100. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775586&dopt=Abstract
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Role of the small GTPase Rho in modulation of the inwardly rectifying potassium channel Kir2.1. Author(s): Jones SV. Source: Molecular Pharmacology. 2003 October; 64(4): 987-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500755&dopt=Abstract
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Ruthenium red inhibits TASK-3 potassium channel by interconnecting glutamate 70 of the two subunits. Author(s): Czirjak G, Enyedi P. Source: Molecular Pharmacology. 2003 March; 63(3): 646-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606773&dopt=Abstract
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Serum potassium in the crush syndrome victims of the Marmara disaster. Author(s): Sever MS, Erek E, Vanholder R, Kantarci G, Yavuz M, Turkmen A, Ergin H, Tulbek MY, Duranay M, Manga G, Sevinir S, Lameire N; Marmara Earthquake Study Group. Source: Clinical Nephrology. 2003 May; 59(5): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779093&dopt=Abstract
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Severe hyperkalaemia with prescription of potassium-retaining agents in an elderly patient. Author(s): Martin J, Mourton S, Nicholls G. Source: N Z Med J. 2003 August 8; 116(1179): U542. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513088&dopt=Abstract
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Severe livedo vasculitis treated with potassium iodide. Author(s): Abraham Z, Rozenbaum M, Portnoy E, Rosner I. Source: Rheumatology International. 2003 March; 23(2): 96-8. Epub 2003 January 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634944&dopt=Abstract
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Sex and age differences in serum potassium in the United States. Author(s): Wysowski DK, Kornegay C, Nourjah P, Trontell A. Source: Clinical Chemistry. 2003 January; 49(1): 190-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507983&dopt=Abstract
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Should potassium permanganate be used in wound care? Author(s): Anderson I. Source: Nurs Times. 2003 August 5-11; 99(31): 61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677127&dopt=Abstract
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Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes. Author(s): Storey NM, Gomez-Angelats M, Bortner CD, Armstrong DL, Cidlowski JA. Source: The Journal of Biological Chemistry. 2003 August 29; 278(35): 33319-26. Epub 2003 June 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807917&dopt=Abstract
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Stimulation of the sodium pump in the red blood cell by lithium and potassium. Author(s): Glen AI, Bradbury MW, Wilson J. Source: Nature. 1972 October 13; 239(5372): 399-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635303&dopt=Abstract
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Stimulatory effects of chlorzoxazone, a centrally acting muscle relaxant, on large conductance calcium-activated potassium channels in pituitary GH3 cells. Author(s): Liu YC, Lo YK, Wu SN. Source: Brain Research. 2003 January 3; 959(1): 86-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480161&dopt=Abstract
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Stoichiometry of expressed KCNQ2/KCNQ3 potassium channels and subunit composition of native ganglionic M channels deduced from block by tetraethylammonium. Author(s): Hadley JK, Passmore GM, Tatulian L, Al-Qatari M, Ye F, Wickenden AD, Brown DA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 June 15; 23(12): 5012-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832524&dopt=Abstract
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Structural basis of inward rectifying potassium channel gating. Author(s): Loussouarn G, Rose T, Nichols CG. Source: Trends in Cardiovascular Medicine. 2002 August; 12(6): 253-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242048&dopt=Abstract
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Studies on the oligomeric state of the sodium/calcium + potassium exchanger NCKX2. Author(s): Yoo SS, Leach S, Lytton J. Source: Annals of the New York Academy of Sciences. 2002 November; 976: 94-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502543&dopt=Abstract
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Successful management of a heterotopic Caesarean scar pregnancy: potassium chloride injection with preservation of the intrauterine gestation: case report. Author(s): Salomon LJ, Fernandez H, Chauveaud A, Doumerc S, Frydman R. Source: Human Reproduction (Oxford, England). 2003 January; 18(1): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525465&dopt=Abstract
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Suggestive evidence for association of two potassium channel genes with different idiopathic generalised epilepsy syndromes. Author(s): Chioza B, Osei-Lah A, Wilkie H, Nashef L, McCormick D, Asherson P, Makoff AJ. Source: Epilepsy Research. 2002 December; 52(2): 107-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458027&dopt=Abstract
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The antidepressant fluoxetine blocks the human small conductance calcium-activated potassium channels SK1, SK2 and SK3. Author(s): Terstappen GC, Pellacani A, Aldegheri L, Graziani F, Carignani C, Pula G, Virginio C. Source: Neuroscience Letters. 2003 July 31; 346(1-2): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850554&dopt=Abstract
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The benefits of glucose-insulin-potassium for acute myocardial infarction (and some concerns). Author(s): Apstein CS. Source: Journal of the American College of Cardiology. 2003 September 3; 42(5): 792-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957422&dopt=Abstract
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The common single nucleotide polymorphism E23K in K(IR)6.2 sensitizes pancreatic beta-cell ATP-sensitive potassium channels toward activation through nucleoside diphosphates. Author(s): Schwanstecher C, Neugebauer B, Schulz M, Schwanstecher M. Source: Diabetes. 2002 December; 51 Suppl 3: S363-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475776&dopt=Abstract
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The effect of low-dose potassium supplementation on blood pressure in apparently healthy volunteers. Author(s): Naismith DJ, Braschi A. Source: The British Journal of Nutrition. 2003 July; 90(1): 53-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844375&dopt=Abstract
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The effect of nickel sulphate, potassium dichromate, cobalt nitrate and cadmium sulphate on the proteins of cellular contacts and actin skeleton of cultivated human keratinocytes. Author(s): Lozsekova A, Kaiser HW, Danilla T, Buchvald J, Simko J. Source: Bratisl Lek Listy. 2002; 103(7-8): 254-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518998&dopt=Abstract
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The effect of post-transplant spironolactone on daily potassium requirements in patients undergoing autologous stem cell transplantation. Author(s): Demirer T, Ayli M, Dagli M, Fen T, Haznedar R, Ustael N, Ustun T, Oymak A, Ozdel O, Muftuoglu O. Source: Bone Marrow Transplantation. 2002 November; 30(10): 703-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420210&dopt=Abstract
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The effects of magnesium prime solution on magnesium levels and potassium loss in open heart surgery. Author(s): Jian W, Su L, Yiwu L. Source: Anesthesia and Analgesia. 2003 June; 96(6): 1617-20, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760983&dopt=Abstract
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The effects of outward forced convective flow on inward diffusion of potassium across human dentin. Author(s): Pashley DH, Agee K, Zhang Y, Smith A, Tavss EA, Gambogi RJ. Source: Am J Dent. 2002 August; 15(4): 256-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12572645&dopt=Abstract
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The influence of membrane lipid metabolites on lymphocyte potassium channel activity. Author(s): Teisseyre A, Michalak K, Kuliszkiewicz-Janus M. Source: Cellular & Molecular Biology Letters. 2002; 7(4): 1095-109. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511977&dopt=Abstract
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The optimal dose of potassium citrate in the treatment of children with distal renal tubular acidosis. Author(s): Tapaneya-Olarn W, Khositseth S, Tapaneya-Olarn C, Teerakarnjana N, Chaichanajarernkul U, Stitchantrakul W, Petchthong T. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549788&dopt=Abstract
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The prevalence of interstitial cystitis in gynecologic patients with pelvic pain, as detected by intravesical potassium sensitivity. Author(s): Parsons CL, Dell J, Stanford EJ, Bullen M, Kahn BS, Willems JJ. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 1395400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439537&dopt=Abstract
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The Roles of N- and C-terminal determinants in the activation of the Kv2.1 potassium channel. Author(s): Ju M, Stevens L, Leadbitter E, Wray D. Source: The Journal of Biological Chemistry. 2003 April 11; 278(15): 12769-78. Epub 2003 January 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560340&dopt=Abstract
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The vasodilatory action of testosterone: a potassium-channel opening or a calcium antagonistic action? Author(s): Jones RD, Pugh PJ, Jones TH, Channer KS. Source: British Journal of Pharmacology. 2003 March; 138(5): 733-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642373&dopt=Abstract
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The voltage-gated potassium channel KCNQ2 in Taiwanese children with febrile convulsions. Author(s): Chou IC, Tsai FJ, Huang CC, Lin CC, Tsai CH. Source: Neuroreport. 2002 October 28; 13(15): 1971-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395102&dopt=Abstract
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Thyroid uptake and radiation dose after (131)I-lipiodol treatment: is thyroid blocking by potassium iodide necessary? Author(s): Bacher K, Brans B, Monsieurs M, De Winter F, Dierckx RA, Thierens H. Source: European Journal of Nuclear Medicine and Molecular Imaging. 2002 October; 29(10): 1311-6. Epub 2002 July 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12271412&dopt=Abstract
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Total body potassium differs by sex and race across the adult age span. Author(s): He Q, Heo M, Heshka S, Wang J, Pierson RN Jr, Albu J, Wang Z, Heymsfield SB, Gallagher D. Source: The American Journal of Clinical Nutrition. 2003 July; 78(1): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816773&dopt=Abstract
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Two mast cell stabilizers, pemirolast potassium 0.1% and nedocromil sodium 2%, in the treatment of seasonal allergic conjunctivitis: a comparative study. Author(s): Shulman DG. Source: Adv Ther. 2003 January-February; 20(1): 31-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772816&dopt=Abstract
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Two-pore-Domain (KCNK) potassium channels: dynamic roles in neuronal function. Author(s): Talley EM, Sirois JE, Lei Q, Bayliss DA. Source: The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry. 2003 February; 9(1): 46-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580339&dopt=Abstract
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Uncontrolled insulin secretion from a childhood pancreatic beta-cell adenoma is not due to the functional loss of ATP-sensitive potassium channels. Author(s): Hussain K, Cosgrove KE, Shepherd RM, Chapman JC, Swift SM, Smith VV, Kassem SA, Glaser B, Lindley KJ, Aynsley-Green A, Dunne MJ. Source: Endocrine-Related Cancer. 2002 December; 9(4): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542400&dopt=Abstract
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Urinary excretion of sodium and potassium in a screened cohort in Okinawa, Japan. Author(s): Iseki K, Iseki C, Itoh K, Uezono K, Sanefuji M, Ikemiya Y, Fukiyama K, Kawasaki T. Source: Hypertens Res. 2002 September; 25(5): 731-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452326&dopt=Abstract
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Urodynamic study and potassium sensitivity test for women with frequency-urgency syndrome and interstitial cystitis. Author(s): Kuo HC. Source: Urologia Internationalis. 2003; 71(1): 61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845263&dopt=Abstract
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Use of in vitro release of interferon-gamma in the diagnosis of contact allergy to potassium dichromate - a controlled study. Author(s): Trattner A, Akerman L, Lapidoth M, Klein T, Weiss H, Ben Chaim B, David M. Source: Contact Dermatitis. 2003 April; 48(4): 191-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786722&dopt=Abstract
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UV-induced corneal epithelial cell death by activation of potassium channels. Author(s): Wang L, Li T, Lu L. Source: Investigative Ophthalmology & Visual Science. 2003 December; 44(12): 5095-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638703&dopt=Abstract
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Validation of a glucose-insulin-potassium infusion algorithm in hospitalized diabetic patients. Author(s): Bonnier M, Lonnroth P, Gudbjornsdottir S, Attvall S, Jansson PA. Source: Journal of Internal Medicine. 2003 February; 253(2): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542559&dopt=Abstract
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Validity of a self-administered food frequency questionnaire in the 5-year follow-up survey of the JPHC Study Cohort I to assess sodium and potassium intake: comparison with dietary records and 24-hour urinary excretion level. Author(s): Sasaki S, Ishihara J, Tsugane S; JPHC. Source: J Epidemiol. 2003 January; 13(1 Suppl): S102-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701637&dopt=Abstract
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Voltage-gated potassium channel antibodies in limbic encephalitis. Author(s): Pozo-Rosich P, Clover L, Saiz A, Vincent A, Graus F. Source: Annals of Neurology. 2003 October; 54(4): 530-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520669&dopt=Abstract
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What are the roles of the many different types of potassium channel expressed in cerebellar granule cells? Author(s): Mathie A, Clarke CE, Ranatunga KM, Veale EL. Source: Cerebellum (London, England). 2003; 2(1): 11-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12882230&dopt=Abstract
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When is a high potassium not a high potassium? Author(s): Teh MM, Zaman MJ, Brooks AP, Li Voon Chong JS. Source: Journal of the Royal Society of Medicine. 2003 July; 96(7): 354-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835454&dopt=Abstract
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Whole-body skeletal muscle mass: development and validation of total-body potassium prediction models. Author(s): Wang Z, Zhu S, Wang J, Pierson RN Jr, Heymsfield SB. Source: The American Journal of Clinical Nutrition. 2003 January; 77(1): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499326&dopt=Abstract
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CHAPTER 2. NUTRITION AND POTASSIUM Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and potassium.
Finding Nutrition Studies on Potassium The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “potassium” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on potassium: •
Blood pressure and nutrient intake in the United States. Source: McCarron, David A. Morris, Cynthia D. Henry, Holly H. Stanton, John L. Nutrition-today (USA). (Jul-August 1984). volume 19(4) page 14-17, 20-23.
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Diet for keeping blood pressure down. Source: Tufts-University-diet-and-nutrition-letter (USA). (July 1996). volume 14(5) page 6.
Additional consumer oriented references include: •
Effects of adrenergic blockade on serum potassium changes in response to acute insulin-induced hypoglycemia in nondiabetic humans. Author(s): Diabetic Department, Western Infirmary/Gartnavel General Hospital, Glasgow, Scotland, UK. Source: Fisher, B M Thomson, I Hepburn, D A Frier, B M Diabetes-Care. 1991 July; 14(7): 548-52 0149-5992
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Greater potassium intake may lower stroke risk. Source: Anonymous Harv-Heart-Lett. 1999 January; 9(5): 5 1051-5313
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I recently read that potassium supplements can reduce blood pressure. What is your opinion? I have borderline hypertension, which I'm trying to control with diet and exercise. Source: Robb Nicholson, C Harv-Womens-Health-Watch. 1999 January; 6(5): 8 1070910X
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Perioperative management of diabetic subjects. Subcutaneous versus intravenous insulin administration during glucose-potassium infusion. Author(s): Istituto di Clinica Medica Generale, Universita degli Studi di Parma, Italy. Source: Pezzarossa, A Taddei, F Cimicchi, M C Rossini, E Contini, S Bonora, E Gnudi, A Uggeri, E Diabetes-Care. 1988 January; 11(1): 52-8 0149-5992
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Potassium and hypertension. Source: Tobian, L Nutr-Revolume 1988 August; 46(8): 273-83 0029-6643
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Potassium bicarbonate supplementation and calcium metabolism in postmenopausal women: are we barking up the wrong tree? Author(s): USDA Human Nutrition Center on Aging, Tufts University, Boston, MA. Source: Wood, R J Nutr-Revolume 1994 August; 52(8 Pt 1): 278-80 0029-6643
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Potassium supplementation in essential hypertension. Source: Anonymous Nutr-Revolume 1988 August; 46(8): 291-4 0029-6643
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Supplemental dietary potassium reduced the need for antihypertensive drug therapy. Source: Anonymous Nutr-Revolume 1992 May; 50(5): 144-5 0029-6643
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The Canadian Medical Association Journal, vol. XVIII, 1928: The use of sodium chloride, potassium chloride, sodium bromide, and potassium bromide in cases of arterial hypertension which are amenable to potassium chloride. Source: Addison, W L Nutr-Revolume 1988 August; 46(8): 295-6 0029-6643
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The effects of potassium, magnesium, calcium, and fiber on risk of stroke. Author(s): Medical Policlinic, University Hospital, Zurich, Switzerland. Source: Suter, P M Nutr-Revolume 1999 March; 57(3): 84-8 0029-6643
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The role of potassium in elevated blood pressure. Source: Langford, H.G. Nutrition-and-the-M.D (USA). (July 1985). volume 11(7) page 12. potassium circulatory disorders blood pressure disease control sodium feed supplements 0732-0167
The following information is typical of that found when using the “Full IBIDS Database” to search for “potassium” (or a synonym): •
Effect of nutrition in rabbit does. 2: Study of enzyme and mineral plasma profile. Author(s): Padua Univ. (Italy). Dipartimento di Scienze Zootecniche Source: Rizzi, C. Chiericato, G.M. Zani, C. Proceedings-of-the-ASPA-Congress-RecentProgress-in-Animal-Production-Science (Italy). (2001). volume 2 page 469-471.
Additional physician-oriented references include: •
Coupling between voltage sensor activation, Ca2+ binding and channel opening in large conductance (BK) potassium channels. Author(s): Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
[email protected] Source: Horrigan, F T Aldrich, R W J-Gen-Physiol. 2002 September; 120(3): 267-305 00221295
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Determination of copper in edible oils by atomic absorption spectrometry after lead piperazinedithiocarbamate solid-phase extraction and potassium cyanide backextraction. Author(s): Department of Chemistry, Faculty of Art and Science, Ondokuz Mayis University, TR-55139 Samsun, Turkiye. Source: Bati, B Cesur, H Anal-Sci. 2002 November; 18(11): 1273-4 0910-6340
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Different gene expression of potassium channels by thyroid hormone and an antithyroid drug between the atrium and ventricle of rats. Author(s): Department of Clinical Pharmacology, Niigata College of Pharmacology, Niigata University, Asahimachi, Niigata, Japan. Source: Ma, M L Watanabe, K Watanabe, H Hosaka, Y Komura, S Aizawa, Y Yamamoto, T Jpn-Heart-J. 2003 January; 44(1): 101-10 0021-4868
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Effects of glucose-insulin-potassium infusion on chronic ischaemic left ventricular dysfunction. Author(s): University of Queensland, Brisbane, Queensland, Australia. Source: Khoury, V K Haluska, B Prins, J Marwick, T H Heart. 2003 January; 89(1): 61-5 1468-201X
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Effects of tetrandrine on calcium and potassium currents in isolated rat hepatocytes. Author(s): Department of Pharmacology,Tongji medical college of Huazhong university of science and technology, Wuhan 430030, Hubei Province, China.
[email protected] Source: Zhou, H Y Wang, F Cheng, L Fu, L Y Zhou, J Yao, W X World-J-Gastroenterol. 2003 January; 9(1): 134-6 1007-9327
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Feasibility of using the potassium titanyl phosphate laser with micromanipulators in robotic neurosurgery: a preliminary study in the rat. Author(s): Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Japan.
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Source: Goto, T Hongo, K Koyama, J Kobayashi, S J-Neurosurg. 2003 January; 98(1): 1315 0022-3085 •
Free energy of a potassium ion in a model of the channel formed by an amphipathic leucine-serine peptide. Author(s): Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, UK. Source: Smith, G R Sansom, M S Eur-Biophys-J. 2002 June; 31(3): 198-206 0175-7571
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Glucose-insulin-potassium solution for acute myocardial infarction. Author(s): Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, New York, NY, USA. Source: Janiger, J L Cheng, J W Ann-Pharmacother. 2002 June; 36(6): 1080-4 1060-0280
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Modulation of the kv3.1b potassium channel isoform adjusts the fidelity of the firing pattern of auditory neurons. Author(s): Department of Pharmacology, Yale University, New Haven, Connecticut 06520, USA. Source: Macica, C M von Hehn, C A Wang, L Y Ho, C S Yokoyama, S Joho, R H Kaczmarek, L K J-Neurosci. 2003 February 15; 23(4): 1133-41 1529-2401
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Protection of potassium channel inhibitors against hypoxia/reoxygenation-induced death of cultured hippocampal neurons. Author(s): Department of Physiology, First Military Medical University, Guangzhou 510515, China. Source: Chen, M Sun, H Y Wang, Y Gao, T M Di-Yi-Jun-Yi-Da-Xue-Xue-Bao. 2002 October; 22(10): 872-4 1000-2588
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Quinine suppresses extracellular potassium transients and ictal epileptiform activity without decreasing neuronal excitability in vitro. Author(s): Division of Neuroscience (Neurophysiology), University of Birmingham School of Medicine, Egbaston, Birmingham B15 2TT, UK.
[email protected] Source: Bikson, M Id Bihi, R Vreugdenhil, M Kohling, R Fox, J E Jefferys, J G Neuroscience. 2002; 115(1): 251-61 0306-4522
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Spectrophotometric method for the determination of nifedipine with 4(methylamino)phenol and potassium dichromate. Author(s): Department of Chemistry, Aligarh Muslim University, India.
[email protected] Source: Rahman, N Hoda, M N Farmaco. 2002 June; 57(6): 435-41 0014-827X
•
Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats. Author(s): 3M Medical Department, Corporate Toxicology, 3M Center 220-2E-02, Saint Paul, MN 55133, USA. Source: Seacat, A M Thomford, P J Hansen, K J Clemen, L A Eldridge, S R Elcombe, C R Butenhoff, J L Toxicology. 2003 February 1; 183(1-3): 117-31 0300-483X
•
The effect of nickel sulphate, potassium dichromate, cobalt nitrate and cadmium sulphate on the proteins of cellular contacts and actin skeleton of cultivated human keratinocytes. Author(s): 1st Department of Dermatovenerology, Faculty of Medicine, Comenius University Bratislava, Slovakia.
[email protected] Source: Lozsekova, A Kaiser, H W Danilla, T Buchvald, J Simko, J Bratisl-Lek-Listy. 2002; 103(7-8): 254-9 0006-9248
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to potassium; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com
•
Minerals ACE Inhibitors (Angiotensin-Converting Enzyme Inhibitors) Source: Prima Communications, Inc.www.personalhealthzone.com Angiotensin-Converting Enzyme (ACE) Inhibitors Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: Prima Communications, Inc.www.personalhealthzone.com Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Clorazepate Dipotassium Source: Healthnotes, Inc.; www.healthnotes.com Glucosamine/Chondroitin Source: Healthnotes, Inc.; www.healthnotes.com Iodine Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Magnesium Hydroxide Source: Healthnotes, Inc.; www.healthnotes.com
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Naproxen/Naproxen Sodium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com Potassium Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Prima Communications, Inc.www.personalhealthzone.com Potassium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10086,00.html Potassium Chloride Source: Healthnotes, Inc.; www.healthnotes.com Potassium-Sparing Diuretics Source: Integrative Medicine Communications; www.drkoop.com Potassium-Sparing Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Spironolactone Source: Healthnotes, Inc.; www.healthnotes.com Spironolactone/Hydrochlorothiazide Alternative names: Aldactazide Source: Prima Communications, Inc.www.personalhealthzone.com Stinging Nettle Alternative names: Urtica dioica, Urtica urens, Nettle Source: Integrative Medicine Communications; www.drkoop.com •
Food and Diet Acorn Squash Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,190,00.html Apples Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,44,00.html Apricots Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,45,00.html Artichoke Source: Healthnotes, Inc.; www.healthnotes.com Asparagus Source: Healthnotes, Inc.; www.healthnotes.com Atemoya Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,232,00.html Avocado Source: Healthnotes, Inc.; www.healthnotes.com Avocados Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,46,00.html Bamboo Shoots Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,233,00.html Bananas Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,47,00.html Beets Source: Healthnotes, Inc.; www.healthnotes.com Beets Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,10,00.html Bluefish Source: Healthnotes, Inc.; www.healthnotes.com Brazil Nuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,115,00.html Broccoflower Source: Healthnotes, Inc.; www.healthnotes.com Broccoli Source: Healthnotes, Inc.; www.healthnotes.com
Nutrition
Broccoli Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,11,00.html Brussels Sprouts Source: Healthnotes, Inc.; www.healthnotes.com Brussels Sprouts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,12,00.html Butterfish Source: Healthnotes, Inc.; www.healthnotes.com Butternut Squash Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,189,00.html Cabbage Source: Healthnotes, Inc.; www.healthnotes.com Cantaloupe Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,125,00.html Carp Source: Healthnotes, Inc.; www.healthnotes.com Catfish Source: Healthnotes, Inc.; www.healthnotes.com Cauliflower Source: Healthnotes, Inc.; www.healthnotes.com Celeriac (Celery Root) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,241,00.html Celery Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,16,00.html Cherries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,49,00.html Chicory Source: Healthnotes, Inc.; www.healthnotes.com Chocolate Source: Healthnotes, Inc.; www.healthnotes.com Chocolate Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,179,00.html Cod Source: Healthnotes, Inc.; www.healthnotes.com Collards Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Greens Source: Healthnotes, Inc.; www.healthnotes.com Dates Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,50,00.html Feingold Diet Source: Healthnotes, Inc.; www.healthnotes.com Figs Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,51,00.html Flounder Source: Healthnotes, Inc.; www.healthnotes.com Halibut Source: Healthnotes, Inc.; www.healthnotes.com Hazelnuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,307,00.html High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com Honey Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
Nutrition
Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,283,00.html Jacob's Cattle Beans Source: Healthnotes, Inc.; www.healthnotes.com Jerusalem Artichoke Source: Healthnotes, Inc.; www.healthnotes.com Jicama Source: Healthnotes, Inc.; www.healthnotes.com Jicama Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,249,00.html Juices Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,127,00.html Kiwi Fruit Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,54,00.html Kohlrabi Source: Healthnotes, Inc.; www.healthnotes.com Kohlrabi Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,319,00.html Kombu Source: Healthnotes, Inc.; www.healthnotes.com Leeks Source: Healthnotes, Inc.; www.healthnotes.com Lentils Source: Healthnotes, Inc.; www.healthnotes.com Lettuce & Other Salad Greens Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com
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Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,196,00.html Lima Beans Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,151,00.html Lobster Source: Healthnotes, Inc.; www.healthnotes.com Melons Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,57,00.html Milk Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,95,00.html Mullet Source: Healthnotes, Inc.; www.healthnotes.com Mushrooms Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,25,00.html Mustard Greens Source: Healthnotes, Inc.; www.healthnotes.com Non-Nutritive and Artificial Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Nuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,84,00.html Okra Source: Healthnotes, Inc.; www.healthnotes.com Okra Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,26,00.html Onions Source: Healthnotes, Inc.; www.healthnotes.com
Nutrition
Onions Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,27,00.html Oranges Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,59,00.html Oyster Mushrooms Source: Healthnotes, Inc.; www.healthnotes.com Papaya Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,60,00.html Parsnips Source: Healthnotes, Inc.; www.healthnotes.com Persimmon Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,63,00.html Pike Source: Healthnotes, Inc.; www.healthnotes.com Pomegranates Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,216,00.html Porcini Mushrooms Source: Healthnotes, Inc.; www.healthnotes.com Potatoes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,270,00.html Prunes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,66,00.html Pumpkin Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,176,00.html
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Quinoa Source: Healthnotes, Inc.; www.healthnotes.com Quinoa Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,74,00.html Radishes Source: Healthnotes, Inc.; www.healthnotes.com Raisins & Currants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,67,00.html Rockfish Source: Healthnotes, Inc.; www.healthnotes.com Romaine Lettuce Source: Healthnotes, Inc.; www.healthnotes.com Rutabagas Source: Healthnotes, Inc.; www.healthnotes.com Rutabagas Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,202,00.html Salmon Source: Healthnotes, Inc.; www.healthnotes.com Salsify Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,260,00.html Sardines Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,317,00.html Seaweed Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,217,00.html Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,288,00.html
Nutrition
Smelt Source: Healthnotes, Inc.; www.healthnotes.com Snow Peas Source: Healthnotes, Inc.; www.healthnotes.com Soy Flour Source: Healthnotes, Inc.; www.healthnotes.com Summer Squash Source: Healthnotes, Inc.; www.healthnotes.com Sweet Peppers Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,40,00.html Tilefish Source: Healthnotes, Inc.; www.healthnotes.com Tomatoes Source: Healthnotes, Inc.; www.healthnotes.com Tomatoes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,41,00.html Turnips Source: Healthnotes, Inc.; www.healthnotes.com Vegetarian Diet Source: Healthnotes, Inc.; www.healthnotes.com Water Source: Healthnotes, Inc.; www.healthnotes.com Wild Rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,178,00.html Winter Squash Source: Healthnotes, Inc.; www.healthnotes.com Yams Source: Healthnotes, Inc.; www.healthnotes.com
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Zucchini Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND POTASSIUM Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to potassium. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to potassium and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “potassium” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to potassium: •
A long-term study on the efficacy of a herbal plant, Orthosiphon grandiflorus, and sodium potassium citrate in renal calculi treatment. Author(s): Premgamone A, Sriboonlue P, Disatapornjaroen W, Maskasem S, Sinsupan N, Apinives C. Source: Southeast Asian J Trop Med Public Health. 2001 September; 32(3): 654-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944733&dopt=Abstract
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A novel 1:1 complex of potassium mikanin-3-O-sulfate with methanol. Author(s): Jiang RW, He ZD, But PP, Chan YM, Ma SC, Mak TC. Source: Chemical & Pharmaceutical Bulletin. 2001 September; 49(9): 1166-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558604&dopt=Abstract
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A patient with sodium- and potassium-losing nephropathy. Author(s): Fulop M.
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Source: The American Journal of the Medical Sciences. 2003 February; 325(2): 93-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589233&dopt=Abstract •
Activation of adenosine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: therapeutic implications for Parkinson's disease. Author(s): Tai KK, Truong DD. Source: Journal of Neuroscience Research. 2002 August 15; 69(4): 559-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210849&dopt=Abstract
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Activation of mitochondrial ATP-sensitive potassium channels increases cell viability against rotenone-induced cell death. Author(s): Tai KK, McCrossan ZA, Abbott GW. Source: Journal of Neurochemistry. 2003 March; 84(5): 1193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603842&dopt=Abstract
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Calcium-sensitive potassium channel inhibitors antagonize genistein- and daidzeininduced arterial relaxation in vitro. Author(s): Nevala R, Paukku K, Korpela R, Vapaatalo H. Source: Life Sciences. 2001 August 10; 69(12): 1407-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531164&dopt=Abstract
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Cefepime versus ticarcillin and clavulanate potassium and aztreonam for febrile neutropenia therapy in high-dose chemotherapy patients. Author(s): Fleming DR, Ziegler C, Baize T, Mudd L, Goldsmith GH, Herzig RH. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2003 June; 26(3): 285-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796602&dopt=Abstract
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Ceramide inhibits the inwardly rectifying potassium current in GH(3) lactotrophs. Author(s): Wu SN, Lo YK, Kuo BI, Chiang HT. Source: Endocrinology. 2001 November; 142(11): 4785-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606445&dopt=Abstract
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Complex ventricular arrhythmia induced by overuse of potassium supplementation in a young male football player. Case report. Author(s): Parisi A, Alabiso A, Sacchetti M, Di Salvo V, Di Luigi L, Pigozzi F. Source: The Journal of Sports Medicine and Physical Fitness. 2002 June; 42(2): 214-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032418&dopt=Abstract
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Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium
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channels. Author(s): Ye D, Zhang D, Oltman C, Dellsperger K, Lee HC, VanRollins M. Source: The Journal of Pharmacology and Experimental Therapeutics. 2002 November; 303(2): 768-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388664&dopt=Abstract •
Developmental expression of a voltage-dependent potassium channel (Kv3.1) in auditory neurons without cochlear input. Author(s): Feng J, Morest DK. Source: Journal of Neuroscience Research. 2001 July 15; 65(2): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438981&dopt=Abstract
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Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet. Author(s): Frassetto L, Morris RC Jr, Sellmeyer DE, Todd K, Sebastian A. Source: European Journal of Nutrition. 2001 October; 40(5): 200-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842945&dopt=Abstract
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Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats. Author(s): Bowen RA, Clandinin MT. Source: Journal of Neurochemistry. 2002 November; 83(4): 764-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421348&dopt=Abstract
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Effect of glucose/insulin infusion and magnesium supplementation on serum and muscle sodium and potassium and muscle [3H]ouabain binding capacity in Type 1 diabetes mellitus. Author(s): Djurhuus MS, Klitgaard NA, Pedersen KK. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2003; 63(2): 93102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751690&dopt=Abstract
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Effect of oral potassium supplementation on QT dispersion in anorexia nervosa. Author(s): Franzoni F, Mataloni E, Femia R, Galetta F. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(6): 653-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162596&dopt=Abstract
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Effect of potassium supplementation on blood pressure in Chinese: a randomized, placebo-controlled trial. Author(s): Gu D, He J, Wu X, Duan X, Whelton PK.
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Source: Journal of Hypertension. 2001 July; 19(7): 1325-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446724&dopt=Abstract •
Effective treatment of seborrheic dermatitis using a low dose, oral homeopathic medication consisting of potassium bromide, sodium bromide, nickel sulfate, and sodium chloride in a double-blind, placebo-controlled study. Author(s): Smith SA, Baker AE, Williams JH. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 February; 7(1): 59-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896746&dopt=Abstract
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Effects of (-)-epigallocatechin-3-gallate, the main component of green tea, on the cloned rat brain Kv1.5 potassium channels. Author(s): Choi BH, Choi JS, Min DS, Yoon SH, Rhie DJ, Jo YH, Kim MS, Hahn SJ. Source: Biochemical Pharmacology. 2001 September 1; 62(5): 527-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585049&dopt=Abstract
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Effects of contamination of blood specimens with liquid potassium-EDTA anticoagulant. Author(s): Davidson DF. Source: Annals of Clinical Biochemistry. 2002 May; 39(Pt 3): 273-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038602&dopt=Abstract
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Effects of high-dose glucose-insulin-potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes. Author(s): Szabo Z, Arnqvist H, Hakanson E, Jorfeldt L, Svedjeholm R. Source: Clinical Science (London, England : 1979). 2001 July; 101(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11410112&dopt=Abstract
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Effects of tetrandrine on calcium and potassium currents in isolated rat hepatocytes. Author(s): Zhou HY, Wang F, Cheng L, Fu LY, Zhou J, Yao WX. Source: World Journal of Gastroenterology : Wjg. 2003 January; 9(1): 134-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508368&dopt=Abstract
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Electrophysiological modulation of cardiomyocytic tissue by transfected fibroblasts expressing potassium channels: a novel strategy to manipulate excitability. Author(s): Feld Y, Melamed-Frank M, Kehat I, Tal D, Marom S, Gepstein L. Source: Circulation. 2002 January 29; 105(4): 522-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815438&dopt=Abstract
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Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium
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metabisulfite. Author(s): Nair B, Elmore AR; Cosmetic Ingredients Review Expert Panel. Source: International Journal of Toxicology. 2003; 22 Suppl 2: 63-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555420&dopt=Abstract •
Genistein inhibits the inward rectifying potassium current in guinea pig ventricular myocytes. Author(s): Chiang CE, Luk HN, Chen LL, Wang TM, Ding PY. Source: Journal of Biomedical Science. 2002 July-August; 9(4): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145529&dopt=Abstract
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High-dose glucose-insulin-potassium after cardiac surgery: a retrospective analysis of clinical safety issues. Author(s): Szabo Z, Hakanson E, Maros T, Svedjeholm R. Source: Acta Anaesthesiologica Scandinavica. 2003 April; 47(4): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694134&dopt=Abstract
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Inactivation of the antibacterial activity of iodine potassium iodide and chlorhexidine digluconate against Enterococcus faecalis by dentin, dentin matrix, type-I collagen, and heat-killed microbial whole cells. Author(s): Portenier I, Haapasalo H, Orstavik D, Yamauchi M, Haapasalo M. Source: Journal of Endodontics. 2002 September; 28(9): 634-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236305&dopt=Abstract
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Inadvertent infusion of a high dose of potassium chloride via a thoracic epidural catheter. Author(s): Litz RJ, Kreinecker I, Hubler M, Albrecht DM. Source: European Journal of Anaesthesiology. 2001 October; 18(10): 697-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11553248&dopt=Abstract
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Inhibition of the potassium current IK(SO), in cerebellar granule cells, by the inhibitors of MEK1 activation, PD 98059 and U 0126. Author(s): Boyd DF, Mathie A. Source: Neuropharmacology. 2002 February; 42(2): 221-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804618&dopt=Abstract
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Inhibitory effects of potassium channel blockers on tetramethylpyrazine-induced relaxation of rat aortic strip in vitro. Author(s): Tsai CC, Lai TY, Huang WC, Liu IM, Cheng JT. Source: Life Sciences. 2002 August 2; 71(11): 1321-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106597&dopt=Abstract
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Kolaviron modulates cellular redox status and impairment of membrane protein activities induced by potassium bromate (KBrO(3)) in rats. Author(s): Farombi EO, Alabi MC, Akuru TO. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 January; 45(1): 63-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11820864&dopt=Abstract
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Measurements in potassium-supplemented athletes during and after hypokinetic and ambulatory conditions. Author(s): Zorbas YG, Kakurin VJ, Kuznetsov NA, Yarullin VL, Andreyev ID, Charapakhin KP. Source: Biological Trace Element Research. 2002 January; 85(1): 1-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11881795&dopt=Abstract
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Modulation of inward rectifier potassium channel by toosendanin, a presynaptic blocker. Author(s): Wang ZF, Shi YL. Source: Neuroscience Research. 2001 July; 40(3): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448512&dopt=Abstract
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Modulation of the inward rectifier potassium channel IRK1 by the Ras signaling pathway. Author(s): Giovannardi S, Forlani G, Balestrini M, Bossi E, Tonini R, Sturani E, Peres A, Zippel R. Source: The Journal of Biological Chemistry. 2002 April 5; 277(14): 12158-63. Epub 2002 January 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809752&dopt=Abstract
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Mutagenicity and DNA-damaging activity caused by decomposed products of potassium sorbate reacting with ascorbic acid in the presence of Fe salt. Author(s): Kitano K, Fukukawa T, Ohtsuji Y, Masuda T, Yamaguchi H. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2002 November; 40(11): 1589-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176085&dopt=Abstract
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Natural modulators of large-conductance calcium-activated potassium channels. Author(s): Nardi A, Calderone V, Chericoni S, Morelli I. Source: Planta Medica. 2003 October; 69(10): 885-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14648389&dopt=Abstract
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Nigella sativa (black cumin) ameliorates potassium bromate-induced early events of carcinogenesis: diminution of oxidative stress. Author(s): Khan N, Sharma S, Sultana S.
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Source: Human & Experimental Toxicology. 2003 April; 22(4): 193-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755470&dopt=Abstract •
Pharmacokinetics and toxicity of bromide following high-dose oral potassium bromide administration in healthy Beagles. Author(s): March PA, Podell M, Sams RA. Source: Journal of Veterinary Pharmacology and Therapeutics. 2002 December; 25(6): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485348&dopt=Abstract
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Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries. Author(s): Cortes SF, Rezende BA, Corriu C, Medeiros IA, Teixeira MM, Lopes MJ, Lemos VS. Source: British Journal of Pharmacology. 2001 July; 133(6): 849-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454658&dopt=Abstract
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Potassium fertilization effects on isoflavone concentrations in soybean [Glycine max (L.) Merr.]. Author(s): Vyn TJ, Yin X, Bruulsema TW, Jackson CJ, Rajcan I, Brouder SM. Source: Journal of Agricultural and Food Chemistry. 2002 June 5; 50(12): 3501-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033818&dopt=Abstract
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Potassium titanyloxalate as analytical reagent for micro-quantitative determination of quercetin. Author(s): Pejic N, Kuntic V, Malesev D. Source: Pharmazie. 2002 March; 57(3): 216-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933857&dopt=Abstract
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Potassium-induced increase in renal kallikrein secretion is attenuated in dissected renal connecting tubules of young spontaneously hypertensive rats. Author(s): Yamanaka M, Hayashi I, Fujita T, Cha SH, Endou H, Higashihara M, Majima M. Source: International Immunopharmacology. 2002 December; 2(13-14): 1957-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12489809&dopt=Abstract
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Redox-sensitive extracellular gates formed by auxiliary beta subunits of calciumactivated potassium channels. Author(s): Zeng XH, Xia XM, Lingle CJ. Source: Nature Structural Biology. 2003 June; 10(6): 448-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740608&dopt=Abstract
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Relationship of urinary sodium/potassium excretion and calcium intake to blood pressure and prevalence of hypertension among older Chinese vegetarians. Author(s): Kwok TC, Chan TY, Woo J. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571663&dopt=Abstract
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Role of ATP sensitive potassium channel on 7-hydroxy flavone induced antinociception and possible association with changes in glycaemic status. Author(s): Venkataramanan PE, Parvathavarthini S, Viswanathan S, Ramaswamy S. Source: Indian J Exp Biol. 2000 November; 38(11): 1172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11395966&dopt=Abstract
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Stretch-activated chloride, potassium, and calcium channels coexisting in plasma membranes of guard cells of Vicia faba L. Author(s): Cosgrove DJ, Hedrich R. Source: Planta. 1991 December; 186(1): 143-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11538499&dopt=Abstract
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Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromatemediated renal oxidative stress and toxicity in Wistar rats. Author(s): Khan N, Sharma S, Alam A, Saleem M, Sultana S. Source: Pharmacology & Toxicology. 2001 June; 88(6): 294-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453368&dopt=Abstract
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Tetramethylpyrazine as potassium channel opener to lower calcium influx into cultured aortic smooth muscle cells. Author(s): Tsai CC, Lai TY, Huang WC, Yang T, Liu IM, Wong KL, Chan P, Cheng JT. Source: Planta Medica. 2003 June; 69(6): 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865978&dopt=Abstract
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Tetrandrine inhibits inward rectifying potassium current in cultured bovine aortic endothelial cells. Author(s): Liu WB, Liu GQ, Xiao H, Mao X, Shi Y, Wu JP. Source: Acta Pharmacologica Sinica. 2000 December; 21(12): 1115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603285&dopt=Abstract
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The effect of low-dose potassium supplementation on blood pressure in apparently healthy volunteers. Author(s): Naismith DJ, Braschi A. Source: The British Journal of Nutrition. 2003 July; 90(1): 53-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844375&dopt=Abstract
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The peripheral antinociceptive effect of resveratrol is associated with activation of potassium channels. Author(s): Granados-Soto V, Arguelles CF, Ortiz MI. Source: Neuropharmacology. 2002 October; 43(5): 917-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384177&dopt=Abstract
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The protective role of thiola and soybean seeds against the genotoxicity induced by potassium dichromate in mice. Author(s): Fahmy MA, Shoman HM, Hassan EE. Source: Mutation Research. 2002 May 27; 517(1-2): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034303&dopt=Abstract
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Tonotopic map of potassium currents in chick auditory hair cells using an intact basilar papilla. Author(s): Pantelias AA, Monsivais P, Rubel EW. Source: Hearing Research. 2001 June; 156(1-2): 81-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377884&dopt=Abstract
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Toxicity of lapachol and isolapachol and their potassium salts against Biomphalaria glabrata, Schistosoma mansoni cercariae, Artemia salina and Tilapia nilotica. Author(s): Lima NM, dos Santos AF, Porfirio Z, Goulart MO, Sant'Ana AE. Source: Acta Tropica. 2002 July; 83(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062792&dopt=Abstract
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UV-induced corneal epithelial cell death by activation of potassium channels. Author(s): Wang L, Li T, Lu L. Source: Investigative Ophthalmology & Visual Science. 2003 December; 44(12): 5095-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638703&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to potassium; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Arteriosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis Source: Integrative Medicine Communications; www.drkoop.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Bulimia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Burns Source: Integrative Medicine Communications; www.drkoop.com Cardiac Arrhythmia Source: Healthnotes, Inc.; www.healthnotes.com Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Coronary Artery Disease Source: Integrative Medicine Communications; www.drkoop.com
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Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Edema Source: Integrative Medicine Communications; www.drkoop.com Fainting Source: Integrative Medicine Communications; www.drkoop.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com Heat Exhaustion Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hyperkalemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypertension Alternative names: High Blood Pressure Source: Prima Communications, Inc.www.personalhealthzone.com Hypothyroidism Source: Healthnotes, Inc.; www.healthnotes.com Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com
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Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Preeclampsia Source: Healthnotes, Inc.; www.healthnotes.com Pregnancy and Postpartum Support Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Pulmonary Edema Source: Integrative Medicine Communications; www.drkoop.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Syncope Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Integrative Medicine Communications; www.drkoop.com Water Retention Source: Integrative Medicine Communications; www.drkoop.com
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Weakness Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Gerson Therapy Alternative names: Gerson dietary regime GDR Gerson method Gerson treatment Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/g.html Schuessler Biochemic System of Medicine Alternative names: biochemic medicine biochemic system of medicine biochemic system of medicines tissue salts therapy Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/s.html
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Chinese Medicine Baifan Alternative names: Alum; Baifan (Bai Fan); Alume Source: Chinese Materia Medica Fengmi Alternative names: Honey; Mel Source: Chinese Materia Medica
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Herbs and Supplements Acebutolol Source: Healthnotes, Inc.; www.healthnotes.com Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Albuterol Source: Healthnotes, Inc.; www.healthnotes.com Alfalfa Alternative names: Medicago sativa Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc.; www.healthnotes.com
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Aloe Alternative names: Aloe vera, Aloe barbadensis, Aloe ferox , Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Source: Integrative Medicine Communications; www.drkoop.com Aloe Vera Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10001,00.html Amiloride Source: Healthnotes, Inc.; www.healthnotes.com Amiloride/Hydrochlorothiazide Alternative names: Moduretic Source: Prima Communications, Inc.www.personalhealthzone.com Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Apium Graveolens Source: Integrative Medicine Communications; www.drkoop.com Atenolol Source: Healthnotes, Inc.; www.healthnotes.com Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Benazepril Source: Healthnotes, Inc.; www.healthnotes.com Benzodiazepines Source: Healthnotes, Inc.; www.healthnotes.com Beta-Adrenergic Blockers Source: Healthnotes, Inc.; www.healthnotes.com Betaxolol Source: Healthnotes, Inc.; www.healthnotes.com Bisacodyl Source: Healthnotes, Inc.; www.healthnotes.com Bisoprolol Source: Healthnotes, Inc.; www.healthnotes.com Blood Pressure Drugs Source: Prima Communications, Inc.www.personalhealthzone.com
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Captopril Source: Healthnotes, Inc.; www.healthnotes.com Cascara Alternative names: Cascara sagrada, Rhamnus purshiani cortex Source: Healthnotes, Inc.; www.healthnotes.com Cascara Sagrada Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10013,00.html Celecoxib Source: Healthnotes, Inc.; www.healthnotes.com Celery Seed Alternative names: Apium graveolens Source: Integrative Medicine Communications; www.drkoop.com Centella Alternative names: Gotu Kola; Centella asiatica (Linn.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Colchicine Source: Healthnotes, Inc.; www.healthnotes.com Cyclosporine Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Alternative names: Taraxacum officinale Source: Integrative Medicine Communications; www.drkoop.com Dandelion Source: Prima Communications, Inc.www.personalhealthzone.com Dandelion Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Digoxin Source: Healthnotes, Inc.; www.healthnotes.com Digoxin Alternative names: Crystodigin, Lanoxicaps, Lanoxin Source: Prima Communications, Inc.www.personalhealthzone.com Diuretics Source: Healthnotes, Inc.; www.healthnotes.com
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Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Docusate Source: Healthnotes, Inc.; www.healthnotes.com Electrolytes Source: Integrative Medicine Communications; www.drkoop.com Enalapril Source: Healthnotes, Inc.; www.healthnotes.com Epinephrine Source: Healthnotes, Inc.; www.healthnotes.com Etodolac Source: Healthnotes, Inc.; www.healthnotes.com Felodipine Source: Healthnotes, Inc.; www.healthnotes.com Fennel Source: Healthnotes, Inc.; www.healthnotes.com Fiber Source: Integrative Medicine Communications; www.drkoop.com Gentamicin Source: Healthnotes, Inc.; www.healthnotes.com Glucosamine Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Glabra Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Haloperidol Source: Healthnotes, Inc.; www.healthnotes.com Heparin Source: Healthnotes, Inc.; www.healthnotes.com
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Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Horsetail Alternative names: Equisetum arvense Source: Healthnotes, Inc.; www.healthnotes.com Horsetail Source: Prima Communications, Inc.www.personalhealthzone.com Ibuprofen Source: Healthnotes, Inc.; www.healthnotes.com Indapamide Source: Healthnotes, Inc.; www.healthnotes.com Indomethacin Source: Healthnotes, Inc.; www.healthnotes.com Ipecac Source: Healthnotes, Inc.; www.healthnotes.com Juniper Alternative names: Juniperus communis Source: Healthnotes, Inc.; www.healthnotes.com Juniper Berry Source: Prima Communications, Inc.www.personalhealthzone.com Kelp Source: Healthnotes, Inc.; www.healthnotes.com Ketorolac Source: Healthnotes, Inc.; www.healthnotes.com Labetalol Source: Healthnotes, Inc.; www.healthnotes.com Lepidium Sp Alternative names: Cress; Lepidium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com
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Licorice Source: Prima Communications, Inc.www.personalhealthzone.com Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lisinopril Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Loop Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Losartan Source: Healthnotes, Inc.; www.healthnotes.com Luffa Alternative names: Luffa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Metoprolol Source: Healthnotes, Inc.; www.healthnotes.com Miscellaneous Preparations Source: Integrative Medicine Communications; www.drkoop.com Moexipril Source: Healthnotes, Inc.; www.healthnotes.com Musa Banana Alternative names: Plantain, Banana; Musa sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Nabumetone Source: Healthnotes, Inc.; www.healthnotes.com Nadolol Source: Healthnotes, Inc.; www.healthnotes.com Neomycin Source: Healthnotes, Inc.; www.healthnotes.com Nettle Source: Integrative Medicine Communications; www.drkoop.com
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Oral Corticosteroids Source: Healthnotes, Inc.; www.healthnotes.com Oxaprozin Source: Healthnotes, Inc.; www.healthnotes.com PABA Source: Healthnotes, Inc.; www.healthnotes.com PABA (Para-Aminobenzoic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Phosphorus Source: Integrative Medicine Communications; www.drkoop.com Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piroxicam Source: Healthnotes, Inc.; www.healthnotes.com Plantago Psyllium Alternative names: Psyllium, Ispaghula; Plantago psyllium/ovata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Potentilla Alternative names: Cinquefoil, Silverweed; Potentilla sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Propranolol Source: Healthnotes, Inc.; www.healthnotes.com Quinapril Source: Healthnotes, Inc.; www.healthnotes.com Quinidine Source: Healthnotes, Inc.; www.healthnotes.com Ramipril Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Rofecoxib Source: Healthnotes, Inc.; www.healthnotes.com
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Ruta Alternative names: Rue; Ruta graveolens L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Salicylates Source: Integrative Medicine Communications; www.drkoop.com Salsalate Source: Healthnotes, Inc.; www.healthnotes.com Senna Alternative names: Cassia senna, Cassia angustifolia Source: Healthnotes, Inc.; www.healthnotes.com Sotalol Source: Healthnotes, Inc.; www.healthnotes.com Spanish Licorice Alternative names: Licorice Source: Integrative Medicine Communications; www.drkoop.com Stimulant Laxatives Source: Integrative Medicine Communications; www.drkoop.com Sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Sulindac Source: Healthnotes, Inc.; www.healthnotes.com Syzygium Clove Alternative names: Clove, Jamun; Syzygium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Taraxacum Officinale Source: Integrative Medicine Communications; www.drkoop.com Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Source: Healthnotes, Inc.; www.healthnotes.com Tetracyclines Source: Prima Communications, Inc.www.personalhealthzone.com
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Theophylline/Aminophylline Source: Healthnotes, Inc.; www.healthnotes.com Thiazide Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Thiazide Diuretics Source: Prima Communications, Inc.www.personalhealthzone.com Thioridazine Source: Healthnotes, Inc.; www.healthnotes.com Timolol Source: Healthnotes, Inc.; www.healthnotes.com Tobramycin Source: Healthnotes, Inc.; www.healthnotes.com Triamterene Source: Healthnotes, Inc.; www.healthnotes.com Triamterene/Hydrochlorothiazide Alternative names: Dyazide, Maxzide Source: Prima Communications, Inc.www.personalhealthzone.com Trimethoprim Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim/Sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Trimethoprim/Sulfamethoxazole Alternative names: Bactrim, Cotrim, Septra, Sulfatrim Source: Prima Communications, Inc.www.personalhealthzone.com Uricosuric Agents Source: Integrative Medicine Communications; www.drkoop.com Urtica Dioica Source: Integrative Medicine Communications; www.drkoop.com Urtica Urens Source: Integrative Medicine Communications; www.drkoop.com Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON POTASSIUM Overview In this chapter, we will give you a bibliography on recent dissertations relating to potassium. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “potassium” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on potassium, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Potassium ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to potassium. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Voltage-Gated Potassium Channel Beta Subunits and the Chaperone Hypothesis by Connor, Jolien X.; PhD from The University of Wisconsin - Madison, 2002, 186 pages http://wwwlib.umi.com/dissertations/fullcit/3072734
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Voltage-Gated Potassium Channels in Porcine Granulosa Cells: Function and Regulation by Li, Yan; PhD from Kansas State University, 2003, 87 pages http://wwwlib.umi.com/dissertations/fullcit/3090373
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Water-rock Interaction at Small Scales: Studies with Lattice Boltzmann Modeling and Strontium Isotopes in a Potassium-Metasomatized Tuff by Fritz, Diane Elizabeth; PhD from University of Colorado at Boulder, 2002, 131 pages http://wwwlib.umi.com/dissertations/fullcit/3074741
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Whole-Rock Dating of Young Extrusives by the Potassium-Argon Method by Baksi, Ajoy K.; AdvDeg from University of Toronto (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK09115
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A Comparison of Techniques for Estimating the Amount of Fat in the Human Body; and Regression Equations for Predicting the Amount of Potassium in the Human Body by Murphy, Harvey Frank, PhD from University of Illinois at Urbana-champaign, 1967, 149 pages http://wwwlib.umi.com/dissertations/fullcit/6711890
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A Potassium-Argon Geochronological Investigation of the Andean Mobile Belt of North-Central Chile by Quirt, G. Stewart; PhD from Queen's University at Kingston (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK13031
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A Rubidium-Strontium and Potassium-Argon Isotopic Age Investigation Within the Superior Province of the Precambrian Canadian Shield by Purdy, John W; AdvDeg from University of Toronto (Canada), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK01845
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A Test of the Charge Density Wave Model of Potassium Using the Induced Torque Method by Coulter, Philip George; PhD from Mcmaster University (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK65433
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Accurate Potassium/Argon Dating of and Preservation of Oxygen in Zeolites by Faiia, Anthony Marcoux; PhD from Dartmouth College, 2002, 66 pages http://wwwlib.umi.com/dissertations/fullcit/3059807
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Activation of Calcium-Activated Potassium Channels and Cell Migration by Hepatocyte Growth Factor/scatter Factor in Madin-Darby Canine Kidney Cells by Jin, Min; PhD from East Tennessee State University, 2002, 74 pages http://wwwlib.umi.com/dissertations/fullcit/3083430
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An Examination of the Validity of Hypotheses of Two Theories of Soybean Response to Phosphorus and Potassium (Crop Management, Response Model) by Anderson, Edwin Lewis, PhD from The University of Tennessee, 1991, 113 pages http://wwwlib.umi.com/dissertations/fullcit/9133716
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An Investigation of the Mechanism of Relaxation of Canine Airway Smooth Muscle by the Potassium-sparing Diuretic Amiloride by Krampetz, Ingrid Kim; PhD from The University of Manitoba (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54939
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Argon-40/argon-39 Step Heating of Biotite, Hornblende and Potassium Feldspar from a Zone of Contact Metamorphism, Eldora, Colorado by Berger, Glenn W; PhD from University of Toronto (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK19680
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A-Type Potassium Currents in Gastrointestinal Smooth Muscle by Amberg, Gregory Charles; PhD from University of Nevada, Reno, 2002, 178 pages http://wwwlib.umi.com/dissertations/fullcit/3060369
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Biochemical Characterization of Hydrogen, Potassium-ATPase-Rich Membranes from the Gastric Parietal Cell by Taniguchi, Michiko; MS from University of Southern California, 2002, 59 pages http://wwwlib.umi.com/dissertations/fullcit/1411810
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Characterization of a Potassium-Selective Optode Membrane Implemented Using Reflectance-Mode Spectroscopy by Losicco, Tino Louis; PhD from The University of Memphis, 2003, 73 pages http://wwwlib.umi.com/dissertations/fullcit/3095675
Dissertations 147
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Characterization of Kv 1.4 Potassium Ion Channel Expression after Spinal Cord Injury and Its Association with Oligodendrocyte Precursor Cell Proliferation by Edwards, Lori Marie; PhD from University of Toronto (Canada), 2003, 186 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78415
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Characterization of Mice Lacking Kv4.2, An A-Type Potassium Channel by Jung, Wonil Edward; PhD from Stanford University, 2002, 107 pages http://wwwlib.umi.com/dissertations/fullcit/3040027
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Characterization of Subthreshold-Operating Voltage-Gated Potassium Channels in Brain by Saganich, Michael Joseph; PhD from New York University, 2002, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3035321
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Characterization of the KCSA Potassium Channel from Streptomyces Lividans by Lemasurier, Meredith; PhD from Brandeis University, 2002, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3036423
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Characterizations and Design of Planar Optical Waveguides and Directional Couplers by Two-Step Potassium-Sodium Ion-Exchange in Glass by Albert, Jacques; PhD from Mcgill University (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46131
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Coherence Transfer between the (2)p(12)and (2)p(32) Resonance States in Sodium and Potassium, Induced in Collisions with Noble Gas Atoms Simple Molecules by Niewitecka, Barbara; PhD from University of Windsor (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK14766
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Collisional Relaxation in 5(2)p Potassium Atoms by Berends, Randolph William Derek; PhD from University of Windsor (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL43729
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Collisional Relaxation of Multipole Moments in 42p Potassium Atoms by Skalinski, Piotr; PhD from University of Windsor (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK57333
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Competition in a Cardiac Potassium Ion Channel Pore: A Putative Arrhythmogenic Mechanism by Mullins, Franklin McRay; PhD from Vanderbilt University, 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3058713
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Conversion of Chiral Boronic Esters into Potassium Trifluoroborates: Asymmetric Alkyldifluoroboranes and Their Use in Chiral Secondary Amine Synthesis by Kim, Gyungyoun; PhD from Washington State University, 2002, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3069644
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Development of a Cognitive-Based Teacher Stress Measuring Instrument Validated by Sodium/Potassium Ratios in the Blood by Parlock, Bernard M., PhD from Purdue University, 1984, 67 pages http://wwwlib.umi.com/dissertations/fullcit/8423409
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Differential Responses to Nmda Receptor Activation in Nucleus of the Solitary Tract Neurons: a Putative Role for Transient Potassium Conductances by Leveck, David Eugene; Msc from Queen's University at Kingston (Canada), 2002, 85 pages http://wwwlib.umi.com/dissertations/fullcit/MQ73046
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Differential Sensitivity of Antigen- and Mitogen- Stimulated Human Leucocytes to Prolonged Inhibition of Potassium Transport by Wright, E. Pamela; PhD from University of Ottawa (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK25445
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Diffusion Parameters of Group 1b Elements in Molten Potassium Chloride by Denning, Kenneth Frederick; AdvDeg from The University of Saskatchewan (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK05472
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Dopamine Modulation of Potassium Currents in Pyramidal Neurons of Rat Prefrontal Cortex: Neuroadaptations Following Chronic Cocaine Administration by Dong, Yan; PhD from The Herman M. Finch U. of Health Sciences - the Chicago Medical Sch., 2002, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3061529
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Effect of Drought, Flooding, and Potassium Stress on the Quality and Composition of Root Exudates in Axenic Culture (Agropyron Cristatum) by Henry, Amelia; MS from Utah State University, 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/1413828
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Effects of Mitochondrial Atp-sensitive Potassium Channel Activation on Mitochondrial Membrane Potential and Apoptosis by Gursahani, Hemamalini Ishwar; PhD from University of Kentucky, 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3078397
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Electrode Potentials of Iron, Cobalt, Nickel and Hydrogen in a Near-Eutectic Potassium Chloride-Sodium Chloride-Aluminum Chloride Melt by Skala, Martin; PhD from University of Alberta (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK17691
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Electron Nuclear Double Resonance Studies of Free Radicals Trapped in Irradiated Single Crystals of Sodium Formate and Potassium Hydrogen Bisphenylacetate by Park, John Melvyn; PhD from The University of British Columbia (Canada), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK32542
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Electron Spin Resonance of X- and [Gamma]-Irradiated Potassium Difluoromalonate and Electron Paramagnetic Resonance of Copper (II) Complex with Trifluoroacetate Ligands by Mustafa, Mohammed Rafi; AdvDeg from The University of British Columbia (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK05828
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Electronic Spectra of Single Crystal Potassium Bromide Containing Thallous Ion Impurity by Thorsley, Sheila Anne; PhD from The University of Western Ontario (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK14983
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Equilibria Studies for the Molten Salt Systems, Sodium Chloride-Potassium Chloride-Zirconium Tetrachloride and Sodium Chloride-Potassium ChlorideHafnium Tetrachloride and the Application to the Seperation of Hafnium Tetrachloride from Zirconium Tetrachlo by Kim, Jee Dong; PhD from University of Waterloo (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK19325
Dissertations 149
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Evaluation of ATP-sensitive Potassium Channels in Hypothalamic Responses to Alterations in Glucose Availability by Zhang, Yang; PhD from University of Louisiana at Monroe, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3083016
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Exciplex Tuning and Optical Memory Studies for Dicyanoargentate(I) and Dicyanoaurate(I) Ions Doped in Potassium Chloride Crystals. Extension to Mixed Metal Gold and Silver Systems by Hettiarachchi, Samanthika Ruvinie; PhD from University of Maine, 2002, 228 pages http://wwwlib.umi.com/dissertations/fullcit/3074229
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Exodomain Interactions Amongupar, Seprase, Integrins, and Kv1.3 Potassium Channels: Potential Contribution to Tumor Metastasis by Artym, Vira V.; PhD from Wayne State University, 2002, 127 pages http://wwwlib.umi.com/dissertations/fullcit/3049249
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Experimental Investigation of the Directional Distribution of Potassium(A) X-rays from Electron Conversion in Thulium-169 by Salie, David Lester; PhD from The University of Manitoba (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK13763
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Experimental Investigation of the Structural Phase Transition in Potassium Hexachloroosmate by Martin, Carlos Alberto; PhD from University of Toronto (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK35265
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Experiments on the Application of Lasar Selective Excitation Spectroscopy to the Diagnostics of a Potassium Plasma by Rodrigo, Adolfo B; PhD from University of Toronto (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK13070
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Expression, Roles and Regulation of Potassium Channels in Neuroimmune Cells by Khanna, Rajesh; PhD from University of Toronto (Canada), 2003, 226 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78086
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Fixation and Some Adsorption-Desorption Characteristics of Ammonium and Potassium in Four Ghanaian Soils by Oteng, John William; PhD from University of Guelph (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK31103
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Function and Regulation of Sodium-Potassium-Chloride Cotransporter in Cultured Astrocytes under High Extracellular Potassium Concentration by Su, Gui; PhD from The University of Wisconsin - Madison, 2002, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3049480
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Gaba-Evoked Changes in Brain Extracellular Potassium Ions by Barolet, Alan W; PhD from University of Toronto (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL46314
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Gating Rearrangements in Delayed Rectifier Potassium Channels As Measured by Fluorescence by Mcgrath, Maureen Elisabeth; PhD from University of California, Berkeley, 2002, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3082317
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Genetic and Physiological Studies on Potassium and Nitrogen Uptake and Utilization in Wheat by Woodend, John J; PhD from The University of British Columbia (Canada), 1986 http://wwwlib.umi.com/dissertations/fullcit/NL41774
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Growth and Metabolic Responses of the Bush Bean to Potassium Naphthenates by Fattah, Quazi Abdul; Advdeg from The University of British Columbia (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK05089
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Identification and Characterization of a Drosophila KCNQ Potassium Channel Homolog: Analysis of Alternative Splicing and Temporal Expression Patterns by Foltz, Sheri Marie; MS from Texas A&m University - Kingsville, 2002, 95 pages http://wwwlib.umi.com/dissertations/fullcit/1411841
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Identification and Characterization of Strong Inward Rectifier Potassium Channel (kir2.x) Associated Proteins by Leonoudakis, Dmitri; PhD from University of California, Santa Barbara, 2002, 240 pages http://wwwlib.umi.com/dissertations/fullcit/3073631
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Identification of Potassium Channel Subtypes Mediating the PgE(2)-induced Sensitization of Sensory Neurons and Regulation of Potassium Channel Gene Expression by Chronic Inflammation by Jiang, Xin; PhD from Indiana University, 2003, 197 pages http://wwwlib.umi.com/dissertations/fullcit/3094107
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Influence of Pressure on the Cyclotron Mass of Potassium and Hole Fermi Surface of Antimony by Abd-el-rahman, Afaf; PhD from Mcmaster University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NL24102
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Interaction among Nitrogen, Potassium and Boron and Effects on Critical Concentration of Boron in Tomato, Lycopersicon Esculentum Mill. by Watson, Maurice Earl; PhD from University of Guelph (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK14015
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Interactions between Members of the Alpha-K Family of Scorpion Toxins and Voltage-Gated Potassium Channels by Ellis, Karen Catherine; PhD from University of Maryland, Baltimore, 2002, 206 pages http://wwwlib.umi.com/dissertations/fullcit/3048465
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Internalization of the Kv1.4 Voltage-Dependent Potassium Channel by Jugloff, Denis George Mano; PhD from University of Toronto (Canada), 2002, 172 pages http://wwwlib.umi.com/dissertations/fullcit/NQ69216
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Investigation of the Elastic Properties of Lithium Potassium Sulfate Single Crystals As a Function of Temperature and Pressure by Abu-kharma, Mahmoud Hasan; MSC from Memorial University of Newfoundland (Canada), 2002, 72 pages http://wwwlib.umi.com/dissertations/fullcit/MQ73572
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Kv1.3 and Erg Potassium Channels in Microglia: Regulation by Tyrosine Phosphorylation by Cayabyab, Francisco Sandoval; PhD from University of Toronto (Canada), 2002, 306 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74765
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Lymphocyte Transformation and Potassium Transport by Quastel, Michael R; PhD from University of Ottawa (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK15388
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Mass Spectrometric Investigation of the Equilibrium Gas Phase Solvation Reactions Involving (a) Hydration of the Proton, (b) Hydration of the Potassium Ion, and (c) Solvation of the Ammonium Ion by Ammonia Molecules by Searles, Stuart Kenneth; AdvDeg from University of Alberta (Canada), 1968 http://wwwlib.umi.com/dissertations/fullcit/NK03407
Dissertations 151
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Metamorphic Reactions in the System Potassium Oxide-magnesium OxideAluminum Oxide-Silicon Dioxide-Water at Water Pressures to 10 Kilobars by Bird, Gordon Winslow; PhD from University of Toronto (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK11541
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Modulation of Sodium-Potassium Adenosine Triphosphatase Activity in Rat Brain by Adenosine 3'5'-Monophosphate by Lingham, Russell B; PhD from University of Toronto (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK53101
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Molecular Characterization of the Drosophila Melanogaster Ether-a-go-go-related Potassium Channel (DERG): Alternative Splicing and Transcriptional Regulation by Valadez, Roel, Jr.; Ms from Texas A&m University - Kingsville, 2002, 122 pages http://wwwlib.umi.com/dissertations/fullcit/1408386
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Neutron-Scattering and Magnetic Resonance Investigation of Potassium Hexachloroosmate by Mintz, John David; PhD from University of Toronto (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK38782
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Nuclear Quadrupole Resonance Studies of Cuprous Oxide and Potassium Chloroplatinate by Jeffrey, Kenneth R; Advdeg from University of Toronto (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK03900
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Nuclear Quadrupole Resonance Studies of Displacive Phase Transitions in Potassium and Ammonium Hexabromoplatinate by Wiszniewska, Maria; PhD from University of Toronto (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK25513
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Observation of the Transverse Stern-Gerlach Effect in Neutral Potassium and an Analysis of a Charged Particle Stern Gerlach Experiment by Enga, Eric; AdvDeg from The University of British Columbia (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK05806
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Possible Biochemical Mechanisms Regulating Sodium Ion, Potassium Ion-ATPase in Rat Submandibular Gland by Pon, Douglas James; PhD from University of Toronto (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL43506
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Potassium Evoked Release of Noradrenaline from Rat Hearts by Carpenter, John Richard; PhD from University of Alberta (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK23996
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Potassium Interactions with the (Na+, K+)-ATPase by Drapeau, Pierre; PhD from Mcgill University (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK50433
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Potassium Ion Transport and Adenosine Triphosphate Synthesis in Pea Cotyledon Mitochondria by Hamman, W. M.; PhD from University of Alberta (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK17536
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Potassium Metabolism and Renal Function in Sheep by Cowan, Terence Kenneth Jefferson; PhD from The University of Manitoba (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK14896
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Raman Study of Relaxor Ferroelectrics Potassium Tantalum Niobium Oxide, Lead Magnesium Niobate and Lead Zinc Niobate by Svitelskiy, Oleksiy Vasyl; PhD from Lehigh University, 2003, 187 pages http://wwwlib.umi.com/dissertations/fullcit/3073963
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Reduction of Transient Outward Potassium Current and Hypertrophy in Neonatal Rat Ventricular Myocytes: Role of Calcium-Dependent Signaling Pathways by Kassiri, Zamaneh; PhD from University of Toronto (Canada), 2002, 276 pages http://wwwlib.umi.com/dissertations/fullcit/NQ74730
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Regulation of a Two-Pore Potassium(+) Channel by Multiple Functional Subunits in Caenorhabditis Elegans by Perez De La Cruz, Ignacio; PhD from Massachusetts Institute of Technology, 2002 http://wwwlib.umi.com/dissertations/fullcit/f400769
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Regulation of Calcium-activated Potassium Channels by Transforming Growth Factor Beta1 in Developing Chick Ciliary Ganglion Neurons by Lhuillier, Loic Charles; PhD from University of Houston, 2003, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3085611
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Regulation of Gnrh Pulse Generator Activity: Pubertal Maturation and the Role of Potassium(+/ATP) Channels in Mediating Sensitivity to Metabolic Cues by Harris, Glenn Clarke; PhD from Northwestern University, 2002, 204 pages http://wwwlib.umi.com/dissertations/fullcit/3050532
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Regulation of Large-Conductance, Calcium-Sensitive Potassium Channels by the Nitric Oxide/cyclic GMP Signaling Pathway by Swayze, Richard David; MSC from University of Calgary (Canada), 2002, 188 pages http://wwwlib.umi.com/dissertations/fullcit/MQ72193
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Relation of the Sodium(+)/Potassium(+)-ATPase to Reactive Oxygen Species and Mitogen-activated Protein Kinases by Bair, Angela Mae; MSBS from Medical College of Ohio at Toledo, 2002, 66 pages http://wwwlib.umi.com/dissertations/fullcit/1407771
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Reversal of Neuromuscular Blockade by Exchanging Potassium Ions by Caesium Ions in the Isolated Rat Phrenic Nerve-diaphragm Preparation by Korey, Andrew; PhD from The University of Western Ontario (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK14959
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Role of ATP-Sensitive Potassium Channels in Nitric Oxide and Biological Thiol Modulation of Myometrial Plasma Membrane Potential and Uterine Contractility by Clipson, Thea; PhD from University of Michigan, 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3068840
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Role of the Transient Outward Potassium Current and Action Potential Profile in Cardiac Excitation-Contraction Coupling, Hypertrophy and Failure by Sah, Rajan; PhD from University of Toronto (Canada), 2003, 228 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78083
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Selective Open-Channel Block of KV1 Potassium Channels by SNitrosodithiothreitol (SNDTT) by Brock, Mathew William; PhD from Stanford University, 2003, 214 pages http://wwwlib.umi.com/dissertations/fullcit/3085165
Dissertations 153
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Short-Term and Long-Term Regulation of the Sodium, Potassium-ATPase in Aortic Smooth Muscle Cells by Stretch by Sevieux, Nancy; PhD from Louisiana State University Health Sciences Center, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3073569
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Sodium-potassium Adenosine Triphosphatase Turnover in Human Lens Epithelial Cells by Cui, Guangming; PhD from University of Louisville, 2002, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3062484
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Spin Thermodynamics Applied to the Chlorine Nuclear Quadrupolar Resonance in Potassium Hexachloroosmate(IV) by Singh, Marsha A; PhD from University of Toronto (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39660
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Spin-phonon Transition Probabilities for Chromium(3+) and Iron(3+) in Potassium Cobalticyanide by Weissfloch, C. F; Advdeg from Mcgill University (Canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00283
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Structural and Computational Studies of the Potassium Channel T1 Domain and the Ligand Binding Domain of a Glutamate Receptor by Nanao, Max Harunobu; PhD from University of California, San Diego, 2002, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3036994
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Structural Interactions in the Voltage Sensor of Potassium Channels Derived from Metal Ion Coordination in Ether-a-go-go by Silverman, William Ronald; PhD from University of California, Los Angeles, 2002, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3058506
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Structure and Function of Exocytic Hydrogen, Potassium-ATPase-containing Membranes from Gastric Parietal Cells by Duman, Joseph Gerald; PhD from University of California, Berkeley, 2002, 181 pages http://wwwlib.umi.com/dissertations/fullcit/3082170
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Studies in Potassium-argon Dating by Macintyre, Robert Mitchell; Advdeg from University of Toronto (Canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK01031
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Studies of Prokaryotic Potassium Channel Structures and Regulatory Mechanisms by Roosild, Tarmo P.; PhD from University of California, San Diego, 2002, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3055798
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Studies on (Sodium,Potassium)-ATPase As a Diuretic Receptor For Sulfhydryl Reagents By Banerjee, Shailesh P; PhD from University of Toronto (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK11534
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Studies on the Myosin Nucleoside Triphosphatase and the Actin-Myosin Interaction under the Influence of Calcium and Magnesium at Low Concentrations of Potassium Chloride by Sugden, Edward Arthur; AdvDeg from University of Alberta (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK08127
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Studies on the Potassium Supplying Power of Some Southern Ontario Soils by Richards, John Edmond; PhD from University of Guelph (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK67648
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Superprotonic Phase Transitions in Solid Acids: Parameters Affecting the Presence and Stability of Superprotonic Transitions in the MH(N)XO(4) Family of Compounds (X = Sulfur, Selenium, Phosphorus, Arsenic; M = Lithium, Sodium, Potassium,
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Ammonium, Rubidi by Chisholm, Calum Ronald Inneas; PhD from California Institute of Technology, 2003, 272 pages http://wwwlib.umi.com/dissertations/fullcit/3081243 •
The Beta Gamma Subunits of G Proteins Gate a Potassium Channel by Pivoted Bending of a Transmembrane Segment by Jin, Taihao; PhD from Mount Sinai School of Medicine of New York University, 2003, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3075445
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The Collection, Analysis and Comparison of Human Urine between Sedentary and Conditioned Male Caucasians As to the Variation in Sodium, Potassium and Chloride Composition by Braine, Robert Stephen, EDD from West Virginia University, 1978, 72 pages http://wwwlib.umi.com/dissertations/fullcit/7900860
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The Effect of Potassium on the Effluent-free Bleached Kraft Pulp Mill by Gilbert, Allan Franklin; PhD from University of Toronto (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK35030
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The Effects of Potassium and Magnesium Salts of Aspartic Acid on Strength, Endurance, and Body Composition of Male College-Age Advanced Weightlifters by Bowers, Charles Jefferson, EDD from The University of Mississippi, 1981, 151 pages http://wwwlib.umi.com/dissertations/fullcit/8128090
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The Potassium Induced Increase in Metabolism and the Mechanical Threshold in Frog Skeletal Muscle by Vos, Evert Cornelis; AdvDeg from University of Alberta (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK04989
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The Potassium Peroxydisulfate Promoted Oxidative Decarboxylation of Carboxylic Acids by Osman, Soad Abdel Aziz; AdvDeg from University of Alberta (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06231
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The Presence of Alpha(1) and Alpha(2) Subunits of Sodium(+)/Potassium(+)-ATPase in Cardiac Caveolae by Aynafshar, Behrouz; MSBS from Medical College of Ohio at Toledo, 2002, 58 pages http://wwwlib.umi.com/dissertations/fullcit/1410505
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The Reactions of Potassium, Ethyl Zanthate in Aqueous Solution by Tipman, Norman Robert; AdvDeg from The University of British Columbia (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK08337
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The Role and Regulation of Voltage-Dependent Potassium Ion Channels in Pancreatic Beta-Cells by Macdonald, Patrick Edward; PhD from University of Toronto (Canada), 2003, 259 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78448
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The Sodium(+)/Potassium(+)-ATPase As a Signal Transducer by Haas, Michael Steven; PhD from Medical College of Ohio at Toledo, 2002, 175 pages http://wwwlib.umi.com/dissertations/fullcit/3078911
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The Transmembrane and Intracellular Distribution of Chloride and Potassium in Single Striated Muscle Fibers of the Giant Barnacle by Gayton, David Charles; AdvDeg from The University of British Columbia (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06892
Dissertations 155
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Tissue Injury and Remodeling in Rat Hippocampal Dentate Gyrus Following Sodium-Potassium-ATPase Inhibition by Omar, Ayman I.; PhD from University of Ottawa (Canada), 2002, 227 pages http://wwwlib.umi.com/dissertations/fullcit/NQ76454
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Two Distinct Outward Potassium(+) Conductances Are Simultaneously Activated in Tby-2 Suspension Culture Protoplasts by Crotty, Christopher Mark; PhD from McGill University (Canada), 2002, 125 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78669
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON POTASSIUM Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “potassium” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on potassium, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Potassium By performing a patent search focusing on potassium, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on potassium: •
Agricultural oil processing using potassium hydroxide Inventor(s): Daniels; Ralph S. (Sherman, TX) Assignee(s): Mahoney; Carrie Lee (Southbury, CT) Patent Number: 6,632,952 Date filed: June 17, 1994 Abstract: A method of processing agricultural oil in which non-toxic reagents are used, so that a waste stream is evolved suitable for use as a nutrient source and wherein the non-toxic reagents include nutrient source and wherein the non-toxic reagents include nutrient components whereby the nutrient value of the waste stream is enhanced. A variation of convention refining is detailed in which potassium hydroxide is used as refining caustic instead of conventional sodium hydroxide. The resulting process exhibits improvements in waste wash characteristics, more complete oil recovery, less oil in the soapstock, reduced interlayer formation, more soap removed from the refined oil into the soapstock stream, and a less viscous soapstock. Excerpt(s): This invention involves both the field of agricultural oil refining and the field of nutrient material manufacture. Vegetable oils are natural fats which occur in the seeds of oil-seed plants such as soybean, cotton, corn and sunflower. Other agricultural oils are fish oils, animal fats and mixed vegetable-fish-fats. The oils are solvent extracted and refined for edible use as cooking oil (e.g., Wesson Oil.TM.), shortening (e.g., Crisco.TM.), salad dressings, mayonnaise and margarines. Web site: http://www.delphion.com/details?pn=US06632952__
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Alkali-metal-beta-and beta"-alumina and gallate polycrystalline ceramics and fabrication by a vapor phase method Inventor(s): Fung; Kuan-Zong (Salt Lake City, UT), Jue; Jan-Fong (Salt Lake City, UT), Virkar; Anil Vasudeo (Salt Lake City, UT) Assignee(s): Materials and Systems Research, Inc. (Salt Lake City, UT) Patent Number: 6,632,763 Date filed: December 2, 2002 Abstract: A ceramic composite containing alkali-metal-beta- or beta"-alumina and an oxygen-ion conductor is fabricated by converting alpha-alumina to alkali-metal-beta- or beta"-alumina. A ceramic composite with continuous phases of alpha-alumina and the oxygen-ion conducting ceramic, such as zirconia, is exposed to a vapor containing an alkali-metal oxide, such as an oxide of sodium or potassium. Alkali metal ions diffuse through alkali-metal-beta- or beta"-alumina converted from.alpha.-alumina and oxygen ions diffuse through the oxygen-ion conducting ceramic to a reaction front where alphaalumina is converted to alkali-metal-beta- or beta"-alumina. A stabilizer for alkali-metalbeta"-alumina is preferably introduced into the.alpha.-alumina/oxygen-ion conductor composite or introduced into the vapor used to convert the alpha-alumina to an alkalimetal-beta"-alumina.
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Excerpt(s): This invention relates to the formation of polycrystalline alkali-metal-betaand beta"- alumina ceramics, particularly for use as electrolytes in sodium-sulfur batteries, alkali metal thermoelectric converters (AMTEC) and alkali metal sensors. One of the high-temperature secondary battery systems being investigated as a power source for electric vehicles is the sodium-sulfur battery. These batteries offer a high specific energy and high specific power, both of which are required for electric vehicles. These battery systems may also be potential energy storage devices for electric utilities, where long life and low cost are more important than high specific energy and high specific power. In a sodium-sulfur cell, a liquid anode of metallic sodium and liquid cathode of sulfur or sodium polysulfide are separated by a polycrystalline ceramic electrolyte of either sodium beta- or beta"-Al.sub.2 O.sub.3. The operating temperature is typically between 300 and 400.degree. C. In this battery, sodium ions diffuse during discharge from the anode to the cathode by ionic conduction through the ceramic electrolyte. Usually the electrolyte is in the form of a tube with the liquid sodium anode in the interior of the tube. For high operating efficiency and low battery cost, it is essential that the conductivity of the electrolyte be as high as possible. For this reason, the preferred electrolyte is the sodium beta"- Al.sub.2 O.sub.3, because of its higher ionic conductivity. Web site: http://www.delphion.com/details?pn=US06632763__ •
Aqueous dispersion for chemical mechanical polishing used for polishing of copper Inventor(s): Hattori; Masayuki (Tokyo, JP), Kawahashi; Nobuo (Tokyo, JP), Minamihaba; Gaku (Kanagawa, JP), Motonari; Masayuki (Tokyo, JP), Yano; Hiroyuki (Kanagawa, JP) Assignee(s): JSR Corporation (Tokyo, JP), Kabushiki Kaisha Toshiba (Kawasaki, JP) Patent Number: 6,653,267 Date filed: June 29, 2001 Abstract: The present invention provides an aqueous dispersion for chemical mechanical polishing suitable for polishing of copper, which has a high polishing speed and a low erosion rate with overpolishing. The aqueous dispersion for chemical mechanical polishing of the invention contains a compound having a heterocycle, a surfactant and an oxidizing agent, wherein the compound having a heterocycle and the surfactant are in a weight ratio of 1:10 to 1:0.03. The aqueous dispersion may also contain abrasive particle. The compound having a heterocycle is preferably quinaldic acid, benzotriazole or the like. The surfactant is preferably a sulfonic acid salt such as potassium dodecylbenzenesulfonate or ammonium dodecylbenzenesulfonate, and the oxidizing agent is preferably ammonium persulfate, hydrogen peroxide or the like. The abrasive particle used may be inorganic particle such as colloidal silica, an organic particle such as polymer particle, or an organic/inorganic composite particle comprising a combination thereof. Excerpt(s): The present invention relates to an aqueous dispersion for chemical mechanical polishing (hereunder referred to simply as "aqueous dispersion") that is useful for polishing of copper during manufacture of semiconductor devices. More specifically, it relates to an aqueous dispersion for chemical mechanical polishing that can be suitably used in the wiring formation steps for semiconductor devices that require combinations of fine wiring of about 0.1.mu.m to thick wiring of about 100.mu.m, such as in DRAMs, high-speed logic LSIs and the like. High densification of semiconductor devices has led to advances in micronization of formed wirings in recent years. The damascene method is well known as a technique allowing further
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micronization of wiring. This method involves embedding a wiring material in a groove or the like formed in an insulating material, and then removing the excess wiring material by chemical mechanical polishing to form the desired wiring. High-speed polishing is desired for this method in order to achieve improved yields in the polishing step. When polishing an initial excess film [thickness X (.ANG.)] with the wiring material embedded in the groove at a polishing rate V (.ANG./min), the intended polishing should be achievable in the time X/V (min), but in actual semiconductor device manufacturing steps, wiring material left at sections other than the groove is also removed, such that overpolishing is carried out for a time exceeding X/V (min). Here, overpolishing of the wiring sections can result in formation of pit shapes. Such pitshaped wiring is known as "erosion",and is undesirable since it lowers yields of the semiconductor device. Web site: http://www.delphion.com/details?pn=US06653267__ •
Arthroscopic irrigation solution and method for inhibition of pain and inflammation Inventor(s): Demopulos; Gregory A. (Mercer Island, WA), Herz; Jeffrey M. (Mill Creek, WA), Pierce; Pamela A. (Tiburon, CA) Assignee(s): Omeros Corporation (Seattle, WA) Patent Number: 6,645,168 Date filed: July 12, 2002 Abstract: A method and solution for perioperatively inhibiting a variety of pain and inflammation processes at wounds from general surgical procedures including oral/dental procedures. The solution preferably includes multiple pain and inflammation inhibitory at dilute concentration in a physiologic carrier, such as saline or lactated Ringer's solution. The solution is applied by continuous irrigation of a wound during a surgical procedure for preemptive inhibition of pain and while avoiding undesirable side effects associated with oral, intramuscular, subcutaneous or intravenous application of larger doses of the agents. One preferred solution to inhibit pain and inflammation includes a serotonin.sub.2 antagonist, a serotonin.sub.3 antagonist, a histamine antagonist, a serotonin agonist, a cyclooxygenase inhibitor, a neurokinin.sub.1 antagonist, a neurokinin.sub.2 antagonist, a purinoceptor antagonist, an ATP-sensitive potassium channel opener, a calcium channel antagonist, a bradykinin.sub.1 antagonist, a bradykinin.sub.2 antagonist and a.mu.-opioid agonist. Excerpt(s): The present invention relates to surgical irrigation solutions and methods, and particularly for anti-inflammatory, anti-pain, anti-spasm and anti-restenosis surgical irrigation solutions. Arthroscopy is a surgical procedure in which a camera, attached to a remote light source and video monitor, is inserted into an anatomic joint (e.g., knee, shoulder, etc.) through a small portal incision in the overlying skin and joint capsule. Through similar portal incisions, surgical instruments may be placed in the joint, their use guided by arthroscopic visualization. As arthroscopists' skills have improved, an increasing number of operative procedures, once performed by "open" surgical technique, now can be accomplished arthroscopically. Such procedures include, for example, partial meniscectomies and ligament reconstructions in the knee, shoulder acromioplasties and rotator cuff debridements and elbow synovectomies. As a result of widening surgical indications and the development of small diameter arthroscopes, wrist and ankle arthroscopies also have become routine. Throughout each arthroscopy, physiologic irrigation fluid (e.g., normal saline or lactated Ringer's) is flushed continuously through the joint, distending the joint capsule and removing operative
Patents 161
debris, thereby providing clearer intra-articular visualization. U.S. Pat. No. 4,504,493 to Marshall discloses an isomolar solution of glycerol in water for a non-conductive and optically clear irrigation solution for arthroscopy. Web site: http://www.delphion.com/details?pn=US06645168__ •
Carbon-based adsorption powder containing cupric chloride Inventor(s): El-Shoubary; Youssef (North Brunswick, NJ), Maes; Rudy (Easton, PA), Seth; Subash C. (Watchung, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,638,347 Date filed: July 10, 2001 Abstract: A carbon-based, adsorption powder containing an effective amount of cupric chloride suitable for removing mercury from a high temperature, high moisture gas stream, wherein the effective amount of cupric chloride ranges from about 1 to about 45 wt percent. Additional additives, such as potassium permanganate, calcium hydroxide, potassium iodide and sulfur, may be added to the powder to enhance the removal of mercury from the gas stream. Excerpt(s): The present invention relates to an adsorption powder useful for the removal of metal and organic pollutants from gas streams. The adsorption powder is typically useful for treating solid waste contaminates, e.g. contaminated soil treatment by high efficiency incineration. More particularly, the invention relates to the capture of mercury and other metals, dioxins, furans and other organic compounds from high temperature, high moisture gas streams using an adsorption powder containing cupric chloride. Strict standards exist for particulate and total mercury emissions by coal-fired power plants, petroleum refineries, chemical refineries, coal fired furnaces, trash burning facilities, incinerators, metallurgical operations, thermal treatment units and other particulate and mercury emitting facilities. These same restrictions apply to mercury vapor, which can enter the atmosphere as a result of low temperature thermal desorption (LTTD) treatment of contaminated soils. These stringent standards exist in order to protect the environment and the community. When mercury-containing gases are released, the gases disperse and mercury is deposited over a wide area. The dispersed mercury can accumulate in the soil or water supplies, where it may be incorporated into the food chain. Mercury is extremely harmful to aquatic life and ultimately to the humans who consume mercury-contaminated plants and animals. It is necessary, therefore, to have a safe and effective method of eliminating mercury from the environment. Web site: http://www.delphion.com/details?pn=US06638347__
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Ceramic carrier and ceramic catalyst body Inventor(s): Andou; Yosiyasu (Kakamigahara, JP), Nakanishi; Tomohiko (Kariya, JP), Yamada; Masanori (Nishio, JP) Assignee(s): Denso Corporation (Aichi-Pref., JP), Nippon Soken, Inc. (Aichi, JP) Patent Number: 6,649,563 Date filed: June 4, 2001
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Abstract: A ceramic carrier and ceramic catalyst body used as NO.sub.x purification catalysts for lean burn engines, which are inexpensive, exhibit high temperature durability and can maintain their catalytic function for extended periods. The ceramic carrier has a diffusion-inhibiting layer formed on the surface of a cordierite honeycomb structure, to inhibit diffusion of alkali metals, alkaline earth metals, etc. carried as NO.sub.x storage materials. The diffusion-inhibiting layer is composed of a ceramic material such as Y.sub.2 O.sub.3, NiO or CeO.sub.2 which does not react with alkali metals or alkaline earth metals at temperatures of up to 1000.degree. C. and has a melting point of higher than 1000.degree. C., and the diffusion-inhibiting layer inhibits diffusion of catalyst components such as potassium into the interior to prevent their reaction with cordierite, so that the durability is greatly enhanced without reducing catalytic performance. Excerpt(s): The present invention relates to an exhaust gas purification catalyst for the purification of exhaust gas emitted from internal combustion engines of automobiles and the like and, specifically, it relates to a ceramic carrier which is ideal as a carrier for an exhaust gas purification catalyst in a lean burn engine or diesel engine, and to a ceramic catalyst body comprising it. On the other hand, exhaust gas temperatures have also been increasing in recent years, making it important to improve the high temperature durability of exhaust gas purification catalysts. Incidentally, catalysts with alkali metals loaded as NO.sub.x storage materials on cordierite carriers have been associated with the problem of reduced NO.sub.x storage capacity and cordierite carrier impairment under higher exhaust gas temperatures. This is attributed to the fact that the alkali metal easily penetrates into the porous coating layer of.gamma.-alumina and reacts with the Si in the cordierite; as a measure against this, Japanese Unexamined Patent Publication HEI No. 10-165817 proposes using a carrier made of a low thermal expansion material containing no Si, instead of a cordierite carrier. However, of the.alpha.-alumina, zirconia, titania, titanium phosphate, aluminum titanate, stainless steel and Fe--Al--Cr alloy mentioned as examples in Japanese Unexamined Patent Publication HEI No. 10-165817, only the very highly dense (heavy) aluminum titanate exhibits a sufficiently low thermal expansion coefficient for practical use. Aluminum titanate, however, is poorly suited given the trend toward lighter weight vehicles and its high cost increases the cost of the metal carrier. Other ceramic materials have high thermal expansion coefficients, and are also impractical from the standpoint of impact resistance. Thus, it is the current situation that no low-cost carrier material with a low thermal expansion coefficient exists as a substitute for cordierite. Web site: http://www.delphion.com/details?pn=US06649563__ •
Cleaning process and cleaning agent for harmful gas Inventor(s): Nawa; Youji (Kanagawa, JP), Otsuka; Kenji (Kanagawa, JP), Takamatsu; Yukichi (Kanagawa, JP), Tonari; Kazuaki (Kanagawa, JP) Assignee(s): Japan Pionics Co., Ltd. (Tokyo, JP) Patent Number: 6,638,489 Date filed: September 21, 2001 Abstract: There are disclosed a process for cleaning a harmful gas which comprises bringing the harmful gas containing as a harmful component, an organosilicon compound represented by the general formula: CH.sub.2 CH--SiR.sub.3, CH.sub.2 CH-Si(OR).sub.3, CH.sub.2 CHCH.sub.2 --SiR.sub.3 or CH.sub.2 CHCH.sub.2 --Si(OR).sub.3, wherein R indicates a saturated hydrocarbon group or an aromatic compound group,
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into contact with a cleaning agent comprising activated carbon adhesively incorporated with at least one species selected from the group consisting of bromine, iodine, a metal bromide and a metal iodide in which the metal is exemplified by copper, lithium, sodium, potassium, magnesium, calcium, strontium, manganese, iron, cobalt, nickel, zinc, aluminum and tin; and a cleaning agent comprising the same. The cleaning process and the cleaning agent enable to practically clean a harmful gas which is exhausted from a semiconductor manufacturing process and the like by the use of a dry cleaning process. Excerpt(s): The present invention relates to a process for cleaning a harmful gas containing as a harmful component, an organosilicon compound represented by the general formula: CH.sub.2 CH--SiR.sub.3, CH.sub.2 CH--Si(OR).sub.3, CH.sub.2 CHCH.sub.2 --SiR.sub.3 or CH.sub.2 CHCH.sub.2 --Si(OR).sub.3, wherein R is a saturated hydrocarbon group or an aromatic compound group; and a cleaning agent therefor. More particularly, it is concerned with a process for cleaning, by dry cleaning process, a harmful gas containing the above-mentioned organosilicon compound which gas is exhausted from a semiconductor manufacturing process or the like; and a cleaning agent therefor. There has been developed in recent years, a wiring material of copper films which has low electric resistance and high electro-migration resistance as a new wiring material taking the place of the wiring material of aluminum films or aluminum alloy films. Plating, sputtering, CVD (chemical vapor deposition) and the like method have been put into practical application as a method of forming copper films. With continuous progress towards three dimensional trend of a device and multi-layer trend of a wiring material, the requirement for flatness of a thin film is steadily growing. Thus, there is expected the advancement of film forming technique by CVD method which technique is capable of forming a thin film meeting the requirements of favorable step coverage and a design rule of 0.13.mu.m or less. In regard to copper film formation by means of CVD method, research and investigation have been made on a method in which any of various solid CVD feed materials is sublimed by being kept at an elevated temperature, and supplied in the form of vapor to a semiconductor manufacturing apparatus. However, disadvantages of the method such as an unreasonably small amount of vapor feed and a low rate of film formation led to unsuccess in commercialization thereof. Nevertheless, development has been made in recent years on CVD feed materials in the form of liquid such as hexafluoroacetylacetone-copper vinyltrimethylsilane [(CF.sub.3 CO).sub.2 CHCu.CH.sub.2 CHSi(CH.sub.3).sub.3 ] or hexafluoroacetylacetone-copper allyltrimethylsilane [(CF.sub.3 CO).sub.2 CHCu.CH.sub.2 CHCH.sub.2 Si(CH.sub.3).sub.3 ], whereby the rate of film formation has been improved to such a level as commercializability. it being so, copper film formation was commenced by the use of the above-mentioned hexafluoroacetylacetonecopper complexes. Web site: http://www.delphion.com/details?pn=US06638489__ •
Combination therapeutic compositions and method of use Inventor(s): Chen; Jin-Long (Foster City, CA), Jaen; Juan C. (Burlingame, CA) Assignee(s): Tularik Inc. (South San Francisco, CA) Patent Number: 6,653,332 Date filed: May 2, 2001 Abstract: The present invention provides pharmaceutical compositions and methods for the treatment of diabetes mellitus using combination therapy. The compositions relate to
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a compound of Formula I and an antidiabetic agent such as sulfonylureas, biguanides, glitazones,.alpha.-glucosidase inhibitors, potassium channel antagonists, aldose reductase inhibitors, glucagon antagonists, activators of RXR, insulin therapy or other anti-obesity agent. The methods include the administration of the combination of compound of Formula I with antidiabetic agent where the two components are delivered in a simultaneous manner, where the compound of Formula I is administered first, followed by the antidiabetic agent, as well as wherein the antidiabetic agent is delivered first followed by the compound of Formula I. Excerpt(s): In general, the present invention relates to pharmaceutical compositions, and more particularly, to pharmaceutical compositions for the treatment of diabetes mellitus using combination therapy. Diabetes mellitus is a term generally used to refer to various pathological states characterized by hyperglycemia and altered metabolism of lipids, carbohydrates and proteins. These conditions are also often associated with other comorbidities, such as obesity and an increased risk of cardiovascular disease. By some estimates, as many as 600,000 new individuals become clinically diabetic every year in the United States. Diabetic conditions are generally classified as either insulindependent diabetes mellitus (IDDM, Type I diabetes) or non-insulin-dependent diabetes mellitus (NIDDM, Type II diabetes). There are also less common clinical pathologies that are associated with diabetic conditions, such as gestational maturity-onset diabetes of youth (MODY), tropical diabetes secondary to chronic pancreatis, diabetes secondary to pancreatic disease or surgery, and diabetes secondary to endocrinopathies. Web site: http://www.delphion.com/details?pn=US06653332__ •
Components coated with an aluminum-silicon alloy Inventor(s): Becker; Andreas (Lachendorf, DE), Frehse; Joachim (Hannover, DE), SesekeKoyro; Ulrich (Isernhagen, DE) Assignee(s): Solvay Pharmaceuticals GmbH (Hannover, DE) Patent Number: 6,648,212 Date filed: December 3, 2001 Abstract: Components composed of aluminum or an aluminum alloy with a coating comprising an aluminum-silicon alloy deposited thereon by applying an alkali metal fluorosilicate and heating the resulting treated material. The alloy layer is effectively protected against re-oxidation by a non-corrosive, alkali metal fluoroaluminate layer (e.g. a potassium fluoroaluminate layer) which forms simultaneously. Excerpt(s): This application is a continuation of international application Ser. No. PCT/EP00/04777, filed May 25, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application No. DE 199 25 301.3, filed Jun. 2, 1999. The invention relates to a process for depositing an aluminum-silicon alloy on aluminum or aluminum alloys, the resulting components which are obtained, and a brazing process. Techniques for brazing components made of aluminum or aluminum alloys are known. The components are joined with the aid of a brazing metal and a flux while being heated. The brazing metal can either be added separately or components plated with brazing metal can be used. The preferred fluxes are potassium fluoroaluminate and/or cesium fluoroaluminate. Web site: http://www.delphion.com/details?pn=US06648212__
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Compositions comprising water soluble copolymer and cesium salt of a carboxylic acid Inventor(s): Benton; William J. (Magnolia, TX), Miller; Edward E. (Plano, TX) Assignee(s): Cabot Corporation (Boston, MA), Fritz Industries, Inc. (Mesquite, TX) Patent Number: 6,656,989 Date filed: May 19, 2000 Abstract: Novel polymer compositions are disclosed, along with their use as well service fluids, for example as completion fluids, work-over fluids or drilling fluids, comprising water soluble copolymers having sulfonate groups and carboxylate groups, along with alkali metal salts of carboxylic acid. Exemplary copolymer has 5 to 95 wt. % structural units derived from 2-acrylamido-2-methylpropanesulfonic acid or salt thereof, and 5 to 95 wt. % structural units derived from acrylic acid or salt thereof. A salt of the polymer may be used, such as the sodium, potassium, ammonium and calcium salts. Exemplary alkali metal salts of the polymer composition include sodium, potassium and cesium salts of formic acid and/or acetic acid in amounts suitable to develop high temperature viscosity suitable for such well servicing fluids. The polymer composition is hydrateble/soluble in a brine of sodium and/or potassium and/or cesium salts of formic and/or acetic acid. Excerpt(s): This invention relates to certain polymer compositions, their preparation and their use as viscosifiers in alkali metal salt solutions which are particularly useful in viscosifying well-drilling fluids for oil field operations at temperatures above 350.degree. F. It is known to use aqueous polysaccharide compositions in well-drilling operations, e.g. in oil and gas wells. Examples of polysaccharides include cellulose derivatives, such as carboxyethylcellulose, carboxymethylcellulose, carboxyrnethylhydroxyethylcellulose, alkylhydroxyalkylcelluloses, alkylcelluloses, alkylcarboxyalkylcelluloses and hydroxyalkylcelluloses (particularly hydroxyethylcellulose); and microbial polysaccharides such as Succinoglycan polysaccharides, Scleroglucan polysaccharides and Xanthan polysaccharides. In order to achieve suitable density for use in well-drilling operations, it is conventional for the known aqueous polysaccharide compositions to include water soluble salts, e.g. as described in UK Patent No. 1,549,734. These salts are typically halide salts (e.g. chlorides and bromides) of mono- or divalent cations, such as sodium, potassium, calcium and zinc, e.g. sodium chloride, potassium chloride, calcium bromide or zinc bromide. Web site: http://www.delphion.com/details?pn=US06656989__
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CRT having an improved internal conductive coating and making the same Inventor(s): Akiyama; Masatoshi (Yotsukaido, JP), Hosotani; Nobuhiko (Mobara, JP), Ito; Hiroshi (Mobara, JP), Matsumoto; Shunichi (Chiba, JP), Nishimura; Kazuyuki (Chiba, JP), Sento; Kiyoshi (Sakura, JP) Assignee(s): Hitachi Device Engineering Co., Ltd. (Mobara, JP), Hitachi, Ltd (Tokyo, JP) Patent Number: 6,639,348 Date filed: March 20, 2000 Abstract: A color cathode ray tube includes an evacuated envelope having a generally rectangular panel portion, a narrow neck portion having a circular cross-section and a
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funnel portion tapering down from a panel-portion side thereof toward a neck-portion side thereof for connecting the panel portion and the neck portion, a three-color phosphor screen formed on an inner surface of the panel portion, an electron gun housed in the neck portion, and an internal conductive film extending from an inner wall of the neck portion to an inner wall of the funnel portion. The funnel portion is provided with a yoke-mounting portion of generally truncated quadrilateral-pyramidal shape for mounting a beam deflection yoke therearound on the neck-portion side of the funnel portion. The internal conductive film is formed of a first part and a second part, the first part is formed of graphite, metallic oxide and potassium silicate, and the second part is formed of graphite and potassium silicate. The first part extends from the neck portion in the vicinity of a forward end of the electron gun to a position in the yokemounting portion spaced a distance in a range of 60 mm to 150 mm from a splice line between the neck portion and the funnel portion, and the second part overlaps with the first part at opposing ends thereof and extends to a vicinity of a seal line between the funnel portion and the panel portion. Excerpt(s): The present invention relates to a cathode ray tube, and in particular to a cathode ray tube having a portion of a funnel portion for mounting a deflection yoke formed in generally truncated quadrilateral-pyramidal shape for the purpose of power saving and having a uniformity in thickness of an internal conductive coating improved in the portion of generally truncated quadrilateral-pyramidal shape to improve reliability of the cathode ray tube. Generally, a cathode ray tube for displaying images or the like is provided with an evacuated envelope comprising a panel portion having a viewing screen formed of phosphor elements coated on an inner surface thereof, a neck portion for housing an electron gun and a funnel portion tapering down from a diameter of the panel portion to a diameter of the neck portion for connecting the panel portion and the neck portion. In a color cathode ray tube for displaying color images, a color viewing screen is formed by coating phosphor elements of a plurality (usually three) of colors on the inner surface of the panel portion, a shadow mask serving as a color selection electrode is closely spaced from the screen and suspended within the panel portion, and an in-line type electron gun for emitting three electron beams is housed in the neck portion. Web site: http://www.delphion.com/details?pn=US06639348__ •
Fuel composition and method for extending the time between turbine washes when burning ash bearing fuel in a turbine Inventor(s): Feitelberg; Alan S. (Niskayuna, NY), Pareek; Vinod Kumar (Niskayuna, NY), Whitehead; Alan (Charlton, NY) Assignee(s): General Electric Company (Schenectady, NY) Patent Number: 6,632,257 Date filed: May 3, 2000 Abstract: The addition of a magnesium compound to an ash bearing fuel results in a reduction in the formation of deposits in the turbine and extending the interval between turbine washes when burning the ash bearing fuel in a turbine compared to burning the ash bearing fuel in a turbine without the addition of a magnesium compound. The additive is desirably effective with ash bearing fuel having less than 0.5 ppm vanadium by weight, less than 1 ppm sodium and potassium combined by weight, and greater than about 25 ppm ash by weight or greater than 2 ppm calcium by weight. The additive
Patents 167
is blended with the ash bearing fuel to give a mass ratio of magnesium to ash of between about 0.5 to 1 and about 3 to 1, and desirably about 1 to 1 on a mass basis after mixing. Excerpt(s): This invention relates generally to fuel compositions for combustion turbines, and more particularly, to fuel compositions and methods for extending the time between turbine washes when burning ash bearing fuels. When combusted in a turbine, various inorganic constituents (ash) in a fuel can affect turbine operation particularly over extended periods of time. Certain constituents in a fuel can cause corrosion of the various parts of the turbine. Other constituents in a fuel can form noncorrosive deposits on the various parts of the turbine. Deposits are often periodically removed with a standard turbine wash cycle. For example, sodium, potassium, and vanadium are of concern in hot corrosion. Turbine manufacturers typically recommend less than 1 ppm (parts per million) by weight of sodium and potassium combined, less than 0.5 ppm by weight of vanadium, and less than 5 ppm other trace metals by weight. In particular, vanadium in a concentration greater than 0.5 ppm by weight forms low melting point vanadium compounds which have been implicated in hot corrosion. Magnesium compounds have been added to fuels having a vanadium content greater than 0.5 ppm by weight to reduce vanadium corrosion in gas turbines. The magnesium compounds react with vanadium to form solid magnesium vanadates, capturing the vanadium in an inert chemical state. Web site: http://www.delphion.com/details?pn=US06632257__ •
Fuel compositions exhibiting improved fuel stability Inventor(s): Orr; William C. (2075 S. University, #240, Denver, CO 80210) Assignee(s): none reported Patent Number: 6,652,608 Date filed: December 8, 1997 Abstract: A fuel composition of the present invention exhibits minimized hydrolysis and increased fuel stability, even after extended storage at 65.degree. F. for 6-9 months. The composition, which is preferably not strongly alkaline (3.0 to 10.5), is more preferably weakly alkaline to mildly acidic (4.5 to 8.5) and most preferably slightly acidic (6.3 to 6.8), includes a lower dialkyl carbonate, a combustion improving amount of at least one high heating combustible compound containing at least one element selected from the group consisting of aluminum, boron, bromine, bismuth, beryllium, calcium, cesium, chromium, cobalt, copper, francium, gallium, germanium, iodine, iron, indium, lithium, magnesium, manganese, molybdenum, nickel, niobium, nitrogen, phosphorus, potassium, palladium, rubidium, sodium, tin, zinc, praseodymium, rhenium, silicon, vanadium, or mixture, and a hydrocarbon base fuel. Excerpt(s): The present invention relates to enhanced structured fuel compositions for use in jet, turbine, diesel, gasoline, and other combustion systems. More particularly, the present invention relates to fuel compositions using viscous hydrocarbons, which are substantially neutral pH, and which employ a silicon based combustion catalyst. International patent application Nos. PCT/US95/02691, PCT/US95/06758, and PCT/US96/09653, are incorporated in their entirety herein by reference, and disclose fuel compositions and combustion techniques for achieving vapor phase combustion based on an enhanced combustion structure ("ECS"). This enhanced combustion structure includes a combustible metallic and free radical generating oxygenated compound. It has been found that such free radical generating oxygenates include C2-
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C12 aldehydes, aldehydic acids, C2-C12 ethers, C1-C15 alcohols, C2-C12 oxides, C3-C15 ketones, ketonic acids, C3-C15 esters, othroesters, C3-C12 diesters, C5-C12 phenols, C5C20 glycol ethers, C2-C12 glycols, C3-C20 alkyl carbonates, C3-C20 dialkyl carbonates, C3-C20 di-carbonates, C1 to C20 organic and inorganic peroxides, hydroperoxides, carboxylic acids, amines, nitrates, di-nitrates, oxalates, phenols, acetic acids, boric acids, orthoborates, hydroxyacids, orthoacids, anhydrides, acetates, acetyls, formic acids, nitrates, di-nitrates, nitro-ethers, which can meet minimum burning velocity (BV) and latent heats of vaporization (LHV) requirements of aforementioned PCT Applications. Specific compounds can be found in detail in Organic Chemistry 6th Ed, T. W. G. Solomons, John Wiley & Sons, N.Y., (1995), Physical Chemistry, 5th Ed, P. W. Atkins, Oxford University Press, U.K. (1994), Physical Organic Chemistry, 2 Ed, N. S. Issacs, John Wiley & Sons, N.Y. (1995) and Lange's Handbook of Chemistry, 14th Ed, J. A. Dean, McGraw-Hill, N.Y. (1992), and their minimum BV/LHV requirements in aforementioned PCT Applications, which are herein by incorporated by reference. Said enhanced combustion structure oxygenates, when in combination with a combustible non-lead metal or non-metal (as set forth below), exhibit high heats of enthalpy capable, improved combustion, thermal efficiency, fuel economy, and power. Of particularly interest to this invention are the enhanced combustion struture oxygenates of symmetrical dialkyl carbonates, especially dimethyl and diethyl carbonates. Web site: http://www.delphion.com/details?pn=US06652608__ •
hKCa3/KCNN3 small conductance calcium activated potassium channel: A diagnostic marker and therapeutic target Inventor(s): Chandy; K. George (Laguna Beach, CA), Fantino; Emmanuelle (Tustin, CA), Gargus; J. Jay (Irvine, CA), Gutman; George (Costa Mesa, CA), Kalman; Katarin (Irvine, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,653,100 Date filed: May 4, 2000 Abstract: The present invention is based on the discovery and cloning of the human small conductance calcium activated potassium channel type 3 (hKCa3/KCNN3) gene, which is expressed in neuronal cells, skeletal muscle, heart, and lymphocytes. Alterations in the hKCa3/KCNN3 gene or its protein product may enhance susceptibility to schizophrenia and/or bipolar disorder. hKCa3/KCNN3 may be involved in neuropsychiatric, neurological, neuromuscular, and immunological disorders. Substantially purified hKCa3/KCNN3 polypeptides and polynucleotides are provided. Antibodies which bind to hKCa3/KCNN3 polypeptides are also disclosed. A method for identifying a compound which affects hKCa3/KCNN3 polynucleotide or polypeptide is provided. A method for diagnosis and determining the prognosis and treatment regimen of a subject having or at risk of having a hKCa3/KCNN3-associated disorder is also provided. A method of treating a subject having or at risk of having an hKCa3/KCNN3-associated disorder by administering a therapeutically effective amount of a polynucleotide encoding SEQ ID NO:2 is also provided. A formulation for administration of hKCa3/KCNN3 to a patient of a therapeutically effective amount of hKCa3/KCNN3 polypeptide is provided. Kits useful for detecting the presence of hKCa3/KCNN3 polypeptide or polynucleotide in a sample from a subject having a hKCa3/KCNN3-associated disorder are provided. Transgenic nonhuman animals having a transgene encoding hKCa3/KCNN3 are also described.
Patents 169
Excerpt(s): This invention relates generally to the field of small conductance calcium activated potassium channels, and more specifically to the diagnosis, study, prevention and treatment of disorders related to these channels. Action potentials in vertebrate neurons are followed by an after hyperpolarization (AHP) that may persist for several seconds and may have profound consequences for the neuronal firing pattern. The AHP has several components, which are distinct are mediated by different calcium activated potassium channels. Small conductance calcium activated potassium channels (SKCa, where "S" represents "small") underlie slow components of the AHP, which are responsible for spike-frequency adaption (Hotson, J. R., and Prince, D. A., J. Neurophysiol. 43:409, 1980). Small conductance channels have a unitary conductance of 4-14ps, are exquisitely sensitive to internal Ca.sup.2+, lack the property of voltage dependence and are blocked by nanomolar concentrations of the natural toxins apamin and scyllatoxin. These channels modulate the firing pattern of neurons via the generation of slow membrane afterhyperpolarizations (Nicoll, R. A., Science 241:545551, 1988). The intermediate channels (IKCa, where "I" represents intermediate conductance) have a conductance of 11-40 pS, are blocked by charybdotoxin and clotrimazol, and are as sensitive to internal Ca.sup.2+ as SKCa channels (Ishii, T. M., et al., Proc. Natl. Acad. Sci. USA 94:11651-11656, 1997; Joiner, W. J., et al., Proc. Natl. Acad Sci. USA 94:11013-11018, 1997). The SKCa are currents that have been described in a wide range of tissues, including brain (Lancaster, B. and Nicoll, R. A., J. Physiol. 389:187203, 1987), peripheral neurons (Goh, J. W., and Pennefather, P. S., J. Physiol. 394:315330,1987), skeletal muscle (Romey, G., and Lazdunski, M., Biochem. Biophys. Res. Commun. 118:669-674, 1984) adrenal chromaffin cells (Neely, A., and Lingle, C. J., J. Physiol. 452:97-131, 1992), leukocytes (Grissmer, S., et al., J. Gen. Physiol. 99:63-84, 1992), erythrocytes (Hamill, O. P., J. Physiol. 319:97P-98P, 1981), colon (Lomax, R. B., et al., Gut 38:243-247, 1996), and airway epithelia (Welsh, M. J., and McCann, J. D., Proc. Natl. Acad. Sci. USA 82:8823-8826, 1985). Certain types of SKCa channels have been distinguished by their sensitivities to the bee venom apamin, whereas other functionally related conductances appear insensitive (Sah, P., and AcLachlan, E. M., 1992, J. Neurophysiol. 74:1772-1776). The distinguishing features of the SKCa channels from the maxi-K calcium activated (BK) potassium channels are the SKCa channels' low conductance (less than 50 pS), the weak or negligible dependence of their activity on membrane voltage, and their high affinity for calcium (EC.sub.50
