Intracellular Regulation of Ion Channels NATO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NATO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The Series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics London and New York C Mathematical and Kluwer Academic Publishers Physical Sciences Dordrecht, Boston and London o Behavioural and Social Sciences E Applied Sciences F Computer and Springer-Verlag Systems Sciences Berlin Heidelberg New York G Ecological Sciences London Paris Tokyo Hong Kong H Cell Biology Barcelona I Global Environmental Change NATo-pea DATABASE The electronic index to the NATO ASI Series provides full bibliographical references (with keywords and/or abstracts) to more than 30000 contributions from international scientists published in all sections of the NATO ASI Series. 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Series H: Cell Biology Vol. 60 Intracellular Regulation of Ion Channels Edited by Martin Morad and Zalman Agus University of Pennsylvania School of Medicine Dept. of Physiology Philadelphia, PA 19104-6085 USA Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest Published in cooperation with NATO Scientific Affairs Division Proceedings of the NATO Advanced Research Workshop on Intracellular Modulation of Cardiac and Neuronal Ion Channels held at II Ciocco, Lucca (Italy) from April 26-30, 1991 ISBN-13: 978-3-642-84630-4 e-ISBN-13:978-3-642-84628-1 001: 10.1007/978-3-642-84628-1 This work is subject to copyright. All rights are reserved, whether the whole or part at the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is per mitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1992 Softcover reprint of the hardcover 1st edition 1992 Typesetting: Camera-ready by authors 31/3140-543210 - Printed on acid-free paper PREFACE Understanding the molecular processes by which ionic channels are regulated is central to the understanding of cellular function. Great advances in understanding these regulatory mechanisms have been recently achieved by the combination of several powerful techniques. Development of the patch clamp technique, ability to access the intracellular channels sites, and genetic manipulation of channel structure have allowed studies of channel function in native membranes. Cloning, sequencing and determining the channel structure and its subunits allows further insight into the regulatory mechanisms of channel function. In planning this symposium, we organized the scientific discussions around specific molecular topics independent of the tissue and species of origin. Clearly, the subject of ion channel regulation is multi-faceted, with a large number of very talented scientists working in the field. The NATO Symposium represented an attempt to bring together these individuals and synthesize and evaluate new ideas and experimental findings. A great deal of novel data was presented, and scientific insight into the molecular processes which regulate ionic channels was furthered. This book gives a synopsis of the scientific presentations and is organized into 3 sections. The first section deals with the diversity of K + channels and their regulation, including structure-function and mechanistic studies. Presentations dealt with the characterization and modulation of a variety ofK+ channels in cardiac and neuronal cells, including ATP dependent K+ channels, Na +- activated K+ channels, delayed rectifier K+ channels and the diversity of their regulation by G-proteins. The second section of the book deals with the molecular understanding of Ca2+c hannel function, its re~lation and genetic manipulation. The role of alternate pathways of regulation of Ca2+ channels, i.e., via protein kinase A phosphorylation, and direct G protein action on the channel (membrane delimited pathway) are considered. Other regulatory mechanisms such as voltage-dependent gating, calcium-dependent inactivation and the role of proteolysis in run-down are also discussed. The third section of the book deals with regulation of other types of channels, including Na +, ct, and If channels. The modulatory effects of cytosolic magnesium and the role of phosphorylation by protein kinases A and C are discussed with reference to epithelial ct channels, neuronal and cardiac Na + channels, and pacemaker If channels. VI It is intended that the book will serve as a reference source for students interested in ion channel regulation, and it is our hope that this subject will become one of the continuing themes of NATO Advanced Workshops (ARW), and that similar symposia will be held in future years. We thank the participants for their time and effort and the excellence of their contributions. Martin Morad Zalman Agus Philadelphia, P A 1991 TABLE OF CONTENTS PART I: Regulation of K+ Channels Page K+ channel diversity 3 o. Pongs Regulation of voltage-activated K+ channels 9 A. M. Brown Gating mechanisms of Shaker potassium channels 15 R. Aldrich Vaccinia virus: A novel expression system for receptors and ion channels 21 A. Karschin Delayed rectification in the heart: Regulation and physiology 27 W.M. Kwok, L.C. Freemen, J. Anumonwo, and R.S. Kass Receptor-dependent modulation of G protein-gated muscarinic K+ channel 43 by arachidonic acid metabolites Y. Kurachi The Na +- activated K+ channel in cardiac cells 53 E. Carmeliet and H.-N. Luk Regulation of the ATP-dependent K+ channel of muscle by ATP and pH 61 N.B. Standen, N.W. Davies, A. Pettit, and P.R. Stanfield Regulation of cardiac ATP-sensitive K+ channels 71 J.N. Weiss, N. Venkatesh, and N.A. Deutsch AT P-sensitive K+ channels: Molecular pharmacology, regulation and role 83 in diseased states M. Lazdunski, M. Fosset, 1. De Weille, E. Honore, C. Mourre PART II: Regulation of Ca2+ Channels Tissue distribution and possible function of the subunits of the L-type 89 calcium channels F. Hofmann, M. Biel, R. Hullin, E. Bosse, V. Flockerzi VIII Phosphorylation and regulation of calcium channels by multiple protein 99 kinases M.M. Hosey, R.M. Brawley, C.F. Chang, L.M. Gutierrez, C. Mundina Weilenmann, J. Ma, and E. Rios Action of the GTP-binding protein Gs on cardiac Ca2+ channels 107 A. Cavalie, T.J.A. Allen, W. Trautwein Membrane-delimited stimulation of heart cell calcium current by fi- 113 adrenergic signal-transducing Gs protein S. Pelzer, Y.M. Shuba, L. Birnbaumer, T.F. McDonald, D.J. Pelzer Participation of a fast G-protein pathway in the fi-adrenergic regulation of 129 cardiac calcium channels: Neither proven nor needed R. Fischmeister, P.-F. Mery, H.C. Hartzell, G. Szabo Kinetics of G-protein mediated action on neuronal Ca2+ channels 141 H.-D. Lux, N. Tokutomi and F. Grassi Identification of G-proteins involved in the inhibition of Ca2+ currents in 153 neuronal and endocrine cells 1. Hescheler, C. Kleuss, C. Ewel, B. Wittig, W. Rosenthal, G. Schultz Voltage-dependent a-adrenergic modulation of Ca2+ channels in peripheral 161 neurons and insulin-secreting cells E. Carbone, A. PolIo, M. Lovallo, G. Aicardi, and E. Sher Voltage-dependent modal gating in cardiac and neuronal L-type calcium 173 channels D. Pietrobon, L. Forti, and P. Hess T-type calcium channels in cardiac muscle: News in kinetics and 181 modulation B. Nilius Calcium regulation of ion channels in neurons 191 R.S. Zucker Role of calpastatin in calcium channel regulation 203 M. Kameyama, A. Kameyama, E. Takano, K. Yazawa, K. Yasui, T. Murachi ct, PART III: Regulation of Na+, and If Channels Structure and modulation of voltage-gated sodium channels 209 W.A. Catterall, T. Scheuer, R. Numann, M. Li, 1. West, B. Murphy, and S. Rossie IX Regulation of the cAMP-dependent chloride current in cardiac ventricular 221 myocytes R.D. Harvey, J.A. Jurevicius, J.R. Hume Magnesium as an intracellular modulator of calcium, potassium and 231 chloride channels Z.S. Agus, E. Kelepouris, 1. Dukes, R. Kasama and M. Morad Cyclic AMP regulation of pacemaker ~) current in heart 241 D. DiFrancesco Subject Index 243 x IN1AACELLU~Afi C~NNE~ F.EGUl",JlN Of ION NATO Advanc:ed Aeseijln;;:h Wortcehop AprH 26 _ April 29.' 99' ·Il. CiOCCa, Tu:.cany.J:taty