Table Of ContentStructure
and Function
in Excitable Cells
Structure
and Function
in Excitable Cells
Edited by
Donald C. Chang
11aylor College of Medicine and Rice University
Houston, Texas
Ichiji Tasaki
National Institute of Mental Health
National Institutes of Health
Bethesda, Maryland, and
The Marine Biological Laboratory
Woods Hole, Massachusetts
William J. Adelman, Jr.
National Institute of Neurological and
Communication Disorders and Stroke
National Institutes of Health at the
Marine Biological Laboratory
Woods Hole, Massachusetts
and
H. Richard Leuchtag
Texas Southern University
Houston, Texas, and
University of Texas Medical Branch
Galveston, Texas
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Structure and function in excitable cells.
Bibliography: p.
Includes index.
1. Excitation (Physiology). 2. Cell membranes. 3. Electrophysiology. I. Chang, Donald
C. II. Title: Excitable cells.
QP363.S8 1983 599'.087 83-13475
ISBN-13: 978-1-4615-9339-3 e-ISBN-13: 978-1-4615-9337-9
DOl: 10.1007/978-1-4615-9337-9
© 1983 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1983
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
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
William J. Adelman, Jr. Louis DeFelice
Laboratory of Biophysics Department of Anatomy
Intramural Research Program Emory University School of Medicine
NINCDS Atlanta, Georgia 30322
National Institutes of Health at
the Marine Biological Laboratory
Woods Hole, Massachusetts 02543
George Eisenman
Department of Physiology
Gilbert Baumann UCLA Medical School
Los Angeles, California 90024
Department of Physiology
Duke University Medical Center
Durham, North Carolina 277 10
Mark H. EUisman
Martin Blank Department of Neurosciences
University of California, San Diego
Department of Physiology School of Medicine
College of Physicians and Surgeons La Jolla, California 92093
Columbia University
New York, New York 10032
Sachiko Endo
Donald C. Chang Department of Biophysics and Biochemistry
Faculty of Science
Department of Physiology
University of Tokyo
Baylor College of Medicine
Bunkyo·ku, Tokyo 113, Japan
Houston, Texas 77030
and Department of Physics
Rice University
Houston, Texas 77251 Harvey M. Fishman
Department of Physiology and Biophysics
University of Texas Medical Branch
D.F. Clapin
Galveston, Texas 77550
Electron Microscopy Unit
Department of Anatomy
Faculty of Health Sciences
Jarl Hagglund
University of Ottawa
of
Ottawa, Ontario Canada KIN 9A9 Department Neurology
and Marine Biological Laboratory University Hospital
Woods Hole, Massachusetts 02543 S-751 23 Uppsala, Sweden
v
vi Contributors
Nobutaka Hirokawa H. Richard Leuchtag
Department of Anatomy and Neurobiology Department of Biology
Washington University School of Medicine Texas Southern University
St. Louis, Missouri 63110 Houston, Texas 77004
and Department of Physiology and Biophysics
University of Texas Medical Branch
Alan Hodge Galveston, Texas 77550
Laboratory of Biophysics
NINCDS
S. Rock Levinson
National Institutes of Health at
the Marine Biological Laboratory Department of Physiology
Woods Hole, Massachusetts 02543 University of Colorado Health Sciences Center
School of Medicine
Denver, Colorado 80262
Kunihiko Iwasa
Laboratory of Neurobiology
James D. Lindsey
National Institutes of Mental Health
Bethesda, Maryland 20205 Department of Neurosciences
and Marine Biological Laboratory University of California, San Diego
Woods Hole, Massachusetts 02543 School of Medicine
La Jolla, California 92093
Michael J. Kell
Gilbert N. Ling
Department of Anatomy
Emory University School of Medicine Department of Molecular Biology
Atlanta, Georgia 30322 Pennsylvania Hospital
Philadelphia, Pennsylvania 19107
B.I. Khodorov
Gen Matsumoto
Vishnevsky Surgery Institute
Electrotechnical Laboratory
Moscow 113093, U.S.S.R.
Tsukuba Science City, Ibaraki 305, Japan
Takaaki Kobayashi Patrick Meares
Department of Biochemistry Chemistry Department
Jikei University University of Aberdeen
Minato-ku, Tokyo 105, Japan Old Aberdeen AB9 2UE, Scotland
J. Metuzals
Harold Lecar
Electron Microscopy Unit
Laboratory of Biophysics
Department of Anatomy
IRP
Faculty of Health Sciences
National Institute of Neurological and
University of Ottawa
Communicative Disorders and Stroke
Ottawa, Ontario, Canada
National Institutes of Health
Bethesda, Maryland 20205 and Marine Biological Laboratory
Woods Hole, Massachusetts 02543
Graham V. Lees Hans Meves
Departement de Biophysique I. Physiologisches Institut der Universitat des Saarlandes
Laboratoire de Neurobiologie Cellulaire du CNRS 6650 Homburg, Saar
F 91190 Gif sur Yvette, France West Gennany
Contributors vii
L. E. Moore Charles L. Schauf
Department of Physiology and Biophysics Department of Physiology
University of Texas Medical Branch Rush University
Galveston, Texas 77550 Chicago, Illinois 60612
Catherine Morris Zadila Suarez-Mata
Department of Biology Centro de Biofisica y Bioquimica
University of Ottawa Instituto Venezolano de Investigaciones Cientificas
Ottawa, Ontario, Canada KIN 9A9 Caracas 10IOA, Venezuela
and Instituto International de Estudios Av anzados
Caracas 1015A, Venezuela
Hiromu Murofushi
Department of Biophysics and Biochemistry
Ichiji Tasaki
Faculty of Science
University of Tokyo Laboratory of Neurobiology
Bunkyo-ku, Tokyo 113, Japan National Institutes of Health
Bethesda, Maryland 20205
and Marine Biological Laboratory
Yves Pichon
Woods Hole, Massachusetts 02543
Departement de Biophysique
Laboratoire de Neurobiologie Cellulaire du CNRS
F 91190 Gif sur Yvette, France Torsten TeoreU
Department of Physiology and Medical Biophysics
Denis Poussart Biomedical Center
Uppsala University
Departement de Genie electrique S-751 23 Uppsala, Sweden
Universite Laval
Quebec GIK 7P4, Canada
Gloria Villegas
Centro de Biofisica y Bioquimica
Francisco Rodriguez
Instituto Venezolano de Investigaciones Cientificas
Centro de Biofisica y Bioquimica Caracas IOIOA, Venezuela
Instituto Venezolano de Investigaciones Cientificas and Instituto International de Estudios A vanzados
Caracas IOIOA, Venezuela Caracas IOI5A, Venezuela
and Instituto International de Estudios A vanzados
Caracas 1015A, Venezuela
Raimondo Villegas
Centro de Biofisica y Bioquimica
Jack Rosenbluth
Instituto Venezolano de Investigaciones Cientificas
Department of Physiology Caracas 10IOA, Venezuela
New York University School of Medicine and Instituto International de Estudios Av anzados
New York, New York 10016 Caracas IOI5A, Venezuela
Hikoichi Sakai Clayton Wiley-Livingston
Department of Biophysics and Biochemistry Department of Pathology
Faculty of Science University of California, San Diego
University of Tokyo School of Medicine
Bunkyo-ku, Tokyo 113, Japan La Jolla, California 92093
John Sandblom Brendan S. Wong
Department of Physiology and Medical Biophysics Department of Physiology
University of Uppsala Baylor College of Dentistry
S-751 23 Uppsala, Sweden Dallas, Texas 75246
Preface
This book is a collection of up-to-date research reviews dealing with various aspects of the
structure and function of excitable cells. Its overall objective is to further the search for a
better understanding of the mechanism of excitation on a structural and physicochemical
basis. The chapters are written by active investigators from a variety of disciplines, repre
senting many different points of view. Their complementary fields of expertise give this
book the rare feature of extraordinary breadth.
Excitability is a fundamental property of many biological systems. The mechanisms
by which nerve impulses are initiated and propagated, and by which rhythmical activities
are produced in nerve, muscle, and cardiac cells, can be fully elucidated only when the
process of excitation is derived from fundamental principles applied to known structural
forms, at both the macroscopic and the molecular level. The problems of excitation are
complex, requiring knowledge of many aspects of cells, including their morphology, elec
trobiology, chemical physics, and biochemistry.
From recent studies of excitable cells a number of new facts about their structure and
function have emerged, so that it became imperative for physiologists interested in studies
of cellular excitation processes to take these findings into consideration. Therefore, several
investigators working at the Marine Biological Laboratory in Woods Hole decided to bring
together for a discussion of these problems a group of electron microscopists, electrophy
siologists, physical chemists and biochemists who have made significant contributions to
our present-day knowledge of biological membranes. Thanks to financial aid from three
U.S. government agencies-the Office of Naval Research, National Institute of Mental
Health, and National Institute of Neurological and Communicative Disorders and Stroke
and the administrative support of the Marine Biological Laboratory, this hope became a
reality: At the International Conference on Structure and Function in Excitable Cells, from
August 31 to September 3, 1981, some 130 researchers from 12 countries gathered in Woods
Hole and exchanged their views on various problems related directly or indirectly to the
cellular excitation mechanism. The present volume is based on the papers given by the
invited lecturers at this Conference, expanded and brought up to date to keep pace with
current developments.
This book consists of four more or less distinct but interrelated parts. Part I deals with
the results of recent studies of the ultrastructure of excitable cells. Among the many new
tools that have become available to provide a clearer view of the structures of these cells is
the increasing application of electron microscopy, in conjunction with rapid freezing,
ix
x Preface
freeze-fracture and new fixation techniques. Ellisman, Lindsey, Wiley-Livingston and
Levinson discuss the differentiation and maintenance of the membrane cytoskeletal struc
ture in nerve. Rosenbluth studies the structure of the node of Ranvier of myelinated nerve
fibers. Metuzals, Clapin and Tasaki present evidence for the existence of a highly organized
structure consisting of different types of filamentous elements intimately connected to the
plasmalemma and for the importance of this structure for the maintenance of excita
bility. The chapter by Hodge and Adelman shows that neurofilaments and neurotubules,
together with cross bridges, form a three-dimensional lattice. Hirokawa's application of
the method of rapid freezing and deep etching provides new views of synaptic and axonal
structures.
Part II, introduced by Adelman, deals mainly with recent electrophysiological findings.
Lecar, Morris and Wong review the work on the minute current pulses, known as "single
channel currents," that have recently been observed in many membrane structures, and
DeFelice and Kell discuss the relation of these to noise and impedance studies. Moore studies
the complex admittance of muscle to observe the linear manifestations of its ion conductances,
while the results of analyses of axon membrane noise are discussed by Pichon, Poussart and
Lees. Chang presents a view of the ion selectivity of the conduction pathway based on a
membrane cortex model. Baumann applies an aggregation model to stochastic processes.
The use of specific neurotoxins to probe membrane behavior is discussed by Meves, who
studies scorpion toxin, and by Khodorov, whose findings relate to batrachotoxin.
In Part III, a physicochemical approach to studies of the cellular excitation mechanisms
is adopted. Tasaki and Iwasa relate their findings on the mechanical responses of the axon
membrane to structural studies of the axolemma-ectoplasm complex. Torsten Teorell, the
founder of the Teorell-Meyer-Sievers theory for ionic membranes, gives an authoritative
historical review of the development of physical chemistry of the membrane. Meares analyzes
nonlinear membrane phenomena that arise from flux coupling. The universal biological
solvent, water, has been replaced with heavy water in the studies of Schauf. Ling studies
the effects of intracellular potassium-ion sorption on the production of cell potentials, and
Eisenman, Sandblom and Hagglund analyze the behavior of narrow ion-conducting channels.
A newly found connection between electrodiffusion and nonlinear waves is explored by
Leuchtag and Fishman, and charged layers at the membrane surface are modeled by Blank.
The fourth part describes various observations emphasizing the importance of protein
molecules in the nerve membrane. Villegas, Villegas, Suarez-Mata and Rodriguez examine
the behavior of reconstituted vesicles containing specific proteins from excitable cells. The
last chapter, by Matsumoto, Murofushi, Endo, Kobayashi and Sakai, points to the necessity
for the presence of microtubules for the maintenance of excitability in squid axon.
This book is founded on the premise that to achieve a clear understanding of the
mechanism of the excitation process, experts from many fields must join forces to attack
the problem. Only by developing improved morphological techniques can we hope to learn
about the structure of the "functional membrane"; only after we gain enough knowledge
about the way ions and solvent molecules interact with protein molecules can we hope to
know the mechanisms that control the flow of ions. We will need a better understanding of
the chemical physics and physical chemistry of polyelectrolyte systems and of the physics
of permeable membranes before we can explain how excitable cells work. Certainly we
need further biochemical analyses to work out the chemical structure of the protein and
phospholipid molecules in the membrane, so that we will know the kind of molecular
apparatus with which we are dealing. The reader will see that the authors emphasize different
aspects of the problem as they see them to be the most important ones. As a result, this
Preface xi
book explores a vast territory. There is very little doubt that some of these explorations will
ultimately prove to be fruitful. We have organized this book in the belief and hope that such
a multidisciplinary approach will help unlock the mystery of the excitation process.
The help of Dr. Arthur B. Callahan of the Office of Naval Research, which has been
particularly valuable both in organizing the conference and preparing this book, is gratefully
acknowledged.
Donald C. Chang
Ichiji Tasaki
William J. Adelman, Jr.
H. Richard Leuchtag
