MEMBRANE TRANSPORT PROCESSES IN ORGANIZED SYSTEMS MEMBRANE TRANSPORT PROCESSES IN ORGANIZED SYSTEMS Edited by Thomas E. Andreoli, M.D. University of Texas Medical School Houston, Texas Joseph F. Hoffman, Ph.D. Yale University School of Medicine New Haven, Connecticut Darrell D. Fanestil, M.D. University of California, San Diego La Jolla, California and Stanley G. Schultz, M.D. University of Texas Medical School Houston Texas PLENUM MEDICAL BOOK COMPANY New York and London Library of Congress Cataloging in Publication Data Physiology of membrane disorders. Selections. Membrane transport processes in organized systems. "This volume is a reprint with minor modifications of parts IV and V of Physiology of membrane disorders, second edition, published by Plenum Medical Book Company in 1986"-T.p. verso. Includes bibliographies and index. 1. Epithelium - Congresses. 2. Biological transport - Congresses. 3. Membranes (Biology) - Congresses. 4. Cell membranes - Congresses. I. Andreoli, Thomas E., 1935- . II. Title. [DNLM: 1. Biological Transport. 2. Ions. 3. Membranes physiology. QS 532.5.M3 P5782ma] QP88.4.P4825 1987 599'.0875 87-18655 ISBN-13: 978-0-306-42698-8 e-ISBN-13: 978-1-4684-5404-8 001: 10.1007/978-1-4684-5404-8 This volume is a reprint with minor modifications of Parts IV and V of Physiology of Membrane Disorders, Second Edition, published by Plenum Medical Book Company in 1986. © 1986,1987 Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition 1987 233 Spring Street, New York, N.Y. 10013 Plenum Medical Book Company is an imprint of Plenum Publishing Corporation All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher Contributors RICHARD W. ALDRICH, PH.D. LINDA S. COSTANZO, PH.D. Postdoctoral Fellow Assistant Professor Section of Molecular Neurobiology Department of Physiology and Biophysics Yale University School of Medicine Medical College of Virginia New Haven, Connecticut 06510 Richmond, Virginia 23289 JOHN M. DIETSCHY, M.D. THOMAS E. ANDREOLI, M.D. Professor of Medicine Edward Randall III Professor and Chairman Department of Internal Medicine Department of Internal Medicine Southwestern Medical School Professor University of Texas Health Science Center Department of Physiology and Cell Biology Dallas, Texas 75235 University of Texas Medical School Houston, Texas 77225 VINCENT E. DIONNE Division of Pharmacology PETER S. ARONSON, M.D. Department of Medicine Associate Professor of Medicine UnivefSlty of California at San Diego and Physiology La Jolla, California 92093 Departments of Physiology and Internal Medicine Yale University School of Medicine ANDREW P. EVAN, PH.D. New Haven, Connecticut 06510 Professor of Anatomy Department of Anatomy Indiana University Medical Center P. DARWIN BELL, PH.D. Indianapolis, Indiana 46223 Assistant Professor of Physiology and Biophysics JOHN G. FORTE, PH.D. Nephrology Research and Training Center and Professor of Physiology Department of Physiology and Biophysics Department of Physiology-Anatomy University of Alabama School of Medicine University of California Birmingham, Alabama 35294 Berkeley, California 94720 GERHARD GIEBISCH, M.D. FRANCISCO BEZANILLA, PH.D. Sterling Professor of Physiology Professor Department of Physiology Department of Physiology Yale University School of Medicme Ahmanson Laboratory of Neurobiology, and New Haven, Connecticut 06510 the Jerry Lewis Neuromuscular Research Center, Umversity of California Medical School EDWARD HAWROT, PH.D. Los Angeles, California 90024 Assistant Professor of Pharmacology Department of Pharmacology WALTER F. BORON, M.D., PH.D. Yale University School of Medicine Assistant Professor New Haven, Connecticut 06510 Department of Physiology Yale University School of Medicine STEVEN C. HEBERT, M.D. New Haven, Connecticut 06510 Assistant Professor of Medicine Division of Nephrology JAMES L. BOYER, M.D. University of Texas Medical School Professor of Medicine Houston, Texas 77225 Director, Liver Study Unit Present address Department of Medicine Harvard Medical School Renal Division Yale UniversIty School of MedIcine Brigham and Women's Hospital New Haven, Connecticut 06510 Boston, Massachusetts 02115 v VI CONTRIBUTORS PETER HESS, M.D. GEORGE DIMITRIE STEPHENSON Research Associate Department of Zoology Department of Physiology La Trobe University Yale University School of Medicine Melbourne, Australia New Haven, Connecticut 06510 JOHN L. STEPHENSON, M.D. H. RONALD KABACK, M.D. Professor of Biomathematics Head, Laboratory of Membrane Biochemistry Department of Physiology Roche Institute of Molecular Biology Cornell University Medical College Roche Research Center New York, New York 10021 Nutley, New Jersey 07110 MARK A. KNEPPER, M.D., PH.D. CHARLES F. STEVENS, M.D., PH.D. Medical Staff Fellow Professor of Physiology National Heart, Lung and Blood Institute Section of Molecular Neurobiology National Institutes of Health Yale University School of Medicine Bethesda, Maryland 20205 New Haven, Connecticut 06510 HANS CHRISTOPH LUTTGAU, M.D. Professor of Physiology RICHARD W. TSIEN, D. PHIL. Department of Cell Physiology Professor of Physiology Ruhr University Department of Physiology Bochum, West Germany Yale University School of Medicine New Haven, Connecticut 06510 TERRY E. MACHEN, PH.D. Associate Professor of Physiology Department of Physiology-Anatomy MICHAEL J. WELSH, M.D. University of California Assistant Professor Berkeley, California 94720 Laboratory of Epithelial Transport and Pulmonary Division Department of Internal Medicine L. GABRIEL NAVAR, PH.D. University of Iowa College of Medicine Professor of Physiology and Biophysics Iowa City, Iowa 52242 Nephrology Research and Training Center and Department of Physiology and Biophysics HENRIK WESTERGAARD, M.D. University of Alabama School of Medicine Birmingham, Alabama 35294 Assistant Professor of Medicine Department of Internal Medicine DON W. POWELL, M.D. Southwestern Medical School Professor and Chief University of Texas Health Science Center Department of Medicine Dallas, Texas 75235 University of North Carolina School of Medicine MICHAEL M. WHITE, PH.D. Chapel Hill, North Carolina 27514 Postdoctoral Researcher Department of Physiology GARY RUDNICK, PH.D. Ahmanson Laboratory of Neurobiology, and Associate Professor of Pharmacology the Jerry Lewis Neuromuscular Research Center, Department of Pharmacology University of California Medical School Yale University School of Medicine Los Angeles, California 90024 New Haven, Connecticut 06510 STANLEY G. SCHULTZ, M.D. ERICH E. WINDHAGER, M.D. Professor and Chairman Professor and Chairman Department of Physiology and Cell Biology Department of Physiology University of Texas Medical School Cornell University Medical College Houston, Texas 77225 New York, New York 10021 Preface Membrane Transport Processes in Organized Systems is a softcover book containing portions of Physiology of Membrane Disorders (Second Edition). The parent volume contains six major sections. This text encompasses the fourth and fifth sections: Transport Events in Single Cells and Transport in Epithelia: Vectorial Transport through Parallel Arrays. We hope that this smaller volume, which deals with transport processes in single cells and in organized epithelia, will be helpful to individuals interested in general physiology, transport in single cells and epithelia, and the methods for studying those transport processes. THOMAS E. ANDREOLI JOSEPH F. HOFFMAN DARRELL D. FANESTIL STANLEY G. SCHULTZ Vll Preface to the Second Edition The second edition of Physiology of Membrane Disorders represents an extensive revision and a considerable expansion ofthe first edition . Yet the purpose of the second edition is identical to that of its predecessor, namely, to provide a rational analysis of membrane transport processes in individual membranes, cells, tissues, and organs, which in tum serves as a frame of reference for rationalizing disorders in which derangements of membrane transport processes play a cardinal role in the clinical expression of disease. As in the first edition, this book is divided into a number of individual, but closely related, sections. Part V represents a new section where the problem of transport across epithelia is treated in some detail. Finally, Part VI, which analyzes clinical derangements, has been enlarged appreciably. THE EDITORS IX Contents PART I: Transport Events in Single Cells CHAPTER 1: Active Transport in Escherichia coli: From Membrane to Molecule H. RONALD KABACK I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. Membrane Vesicles and Active Transport: General Aspects ........................ 3 3. Energetics of Active Transport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 4. Active Transport at the Molecular Level: The ~-Galactoside Transport System ......... 10 5. Summary.. . .. . . .. . . . . . .. . . . . . . . . .. . . . . . . .. . .. . . . .. . . . . . . . . . . . . . . . . . . . . . . . 19 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 CHAPTER 2: Acidification of Intracellular Organelles: Mechanism and Function GARY RUDNICK I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2. Evidence for Acid Interior ................................................... 25 3. Generation of 8pH ......................................................... 27 4. Uses of 8pH .............................................................. 31 5. The Nature of the ATPase ................................................... 34 6. Conclusion ............................................................... 35 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 CHAPTER 3: Intracellular pH Regulation WALTER F. BORON I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 2. Measurement of Intracellular pH .............................................. 39 3. Cellular Buffering Processes ................................................. 40 4. Effect of Externally Applied Weak Acids and Bases .............................. 42 5. Ion-Transport Systems ...................................................... 44 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 CHAPTER 4: Properties of Ionic Channels in Excitable Membranes FRANCISCO BEZANILLA and MICHAEL M. WHITE I. Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 2. How Do You Get a Resting Potential? ......................................... 53 3. How Do You Change the Membrane Potential? .................................. 54 4. Ionic Channels ............................................................ 55 5. The Two-State Model. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 xi xu CONTENTS 6. Real Channels Have More Than Two States ..................................... 57 7. Na+Channels ............................................................ 58 8.K+Channels ............................................................. 61 9. Summary. . . . . . .. . .. . . . . . . . . . . . . . . .. . .. . . . .. . . . . . .. . . .. . . . . . . . . .. . . . . . . . .. 63 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 CHAPTER 5: Ion Movements in Skeletal Muscle in Relation to the Activation of Contraction HANS CHRISTOPH LUTTGAU and GEORGE DIMITRIE STEPHENSON I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 2. The Ultrastructure of the Tubular System in Skeletal Muscle Fibers .................. 65 3. Electrical Properties of the Surface and Tubular Membrane . . . . . . . . . . . . . . . . . . . . . . . . . 66 4. Inward Spread of Excitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 5. Cellular Ca2+ Movements Related to the Activation of Contraction. . . . . . . . . . . . . . . . . . 73 6. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 CHAPTER 6: Excitable Tissues: The Heart RICHARD W. TSIEN and PETER HESS I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 2. Multicellular Structure of the Heart .................................. . . . . . . . . . . 85 3. Electrical Activity in Different Regions of the Heart .............................. 88 4. Na + Channels and Excitability ............................................... 89 5. Ca2 + Channels and Slow Responses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 6. K + Channels Support the Resting Potential and Action Potential Repolarization . . . . . . . . 96 7. Inward Currents and Pacemaker Activity ....................................... 97 8. Adrenergic and Cholinergic Modulation of Cardiac Activity ........................ 99 9. Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 CHAPTER 7: Ion Transport through Ligand-Gated Channels RICHARD W. ALDRICH, VINCENT E. DIONNE, EDWARD HAWROT, and CHARLES F. STEVENS I. Introduction and Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 2. Structure of the Nicotinic AChR .............................................. 109 3. Immunological Approaches to the Study of the Nicotillic AChR ........ . . . . . . . . . . . . . 112 4. Biogenesis, Membrane Localization, and Regulation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 5. Dose-Response ........................................................... 119 6. Kinetics of Channel Gating .................................................. 120 7. AChR Cation SelectlVlty and Permeation ....................................... 123 8. Ligand-Gated Channels Other Than the AChR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 9. An Emerging View of Transmitter-Activated Channels ............................ 126 References . . . . . . . . . . . . . . . . . . . .. .......................................... 127 PART II: Transport in Epithelia: Vectorial Transport through Parallel Arrays CHAPTER 8: Cellular Models of Epithelial Ion Transport STANLEY G. SCHULTZ I. Introduction............. . . . . . . . . .. .. .................................. 135 2. Models of Sodium-and Chlonde-Absorbing Epithelial Cells. . . . . . . . . . . . . . . . . . . . . . . . 136 3. A Model for Active Chloride Secretion by Epithelial Cells ......................... 143 4. Summary. . . . . . . . . . . . . . . . .. .... .. ...................................... 144 References ......... ..................................................... 144 CONTENTS xiii CHAPTER 9: Ion Transport by Gastric Mucosa JOHN G. FORTE and TERRY E. MACHEN I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 2. Organization of Gastric Epithelial Cells ........................................ 151 3. Stimulus-Secretion Coupling in Oxyntic Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 4. Metabolism and Energetics Associated with Gastric HCI Secretion. . . . . . . . . . . . . . . . . . . 155 5. Studies with Isolated Cell Fractions and Membranes .............................. 156 6. Electrophysiological and Tracer Flux Studies of Gastric Ion Transport . . . . . . . . . . . . . . . . 161 7. Summary. . . .. . .•. . . .. . . . .. . .. . . . . . .. .. . .. . .. . .. . . .. . .. . . .. . . .. . . .. . .. . .. .. 169 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 CHAPTER 10: Ion and Water Transport in the Intestine DON W. POWELL I. Introduction.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 2. Models of Intestinal Na + , CI-, and H20 Transport .............................. 175 3. Intestinal Na + and CI- Absorption ........................................... 177 4. Intestinal Na + and CI- Secretion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 5. HCO] , Short-Chain Fatty Acid, and K+ Transport .............................. 184 6. Shunt Pathway and Water Transport ........................................... 187 7. Control of Intestinal Electrolyte Transport ...................................... 188 8. Summary and Conclusions .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 CHAPTER 11: The Uptake of Lipids into the Intestinal Mucosa HENRIK WESTERGAARD and JOHN M. DIETSCHY I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 2. Chemical Species of Lipids That Are Involved during Fat Absorption ................ 213 3. The Barriers to Lipid Absorption in the Intestine ................................. 214 4. Characteristics of the Intestinal Microvillus Membrane Barrier to Lipid Absorption ..... 216 5. Characteristics of the Intestinal U nstirred Water Layer Barrier to Lipid Absorption . . . . . . 217 6. Characteristics of Fatty Acid and Cholesterol Absorption in the Intestine .............. 219 7. Role of Bile Acid Micelles in Facilitating Lipid Absorption in the Intestine ............ 221 8. Nonpolar Lipids ........................................................... 222 9. Summary Description of the Process of Lipid Uptake ............................. 223 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 CHAPTER 12: Mechanisms of Bile Secretion and Hepatic Transport JAMES L. BOYER 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 2. Structural Determinants of Bile Secretory Function ............................... 225 3. Mechanisms of Hepatocellular Water and Electrolyte Secretion ..................... 230 4. Other Primary Driving Forces for Canalicular Bile Secretion (Bile Acid-Independent Secretion) ................................................................ 234 5. Model for Hepatocyte Water and Electrolyte Secretion ............................ 235 6. Physiological Modifiers of Hepatocyte Bile Formation ............................ 236 7. Organic Anion Solute Transport .............................................. 238 8. Lipid Excretion in Bile. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 240 9. Proteins in Bile ............................................................ 242 10. Miscellaneous Substances Found in Bile . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243 11. Bile Duct Function ......................................................... 243 12. Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244 CHAPTER 13: The Regulation of Glomerular Filtration Rate in Mammalian Kidneys L. GABRIEL NAVAR, P. DARWIN BELL, and ANDREW P. EVAN 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253 2. Ultrastructural Considerations ................................................ 254
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