Table Of ContentTHE PROBLEM OF
EXCITABILITY
Electrical Excitability
and Ionic Permeability
of the Nerve Membrane
THE PROBLEM OF
EXCITABILITY
Electrical Excitability
and Ionic Permeability
of the Nerve Membrane
B. I. Khodorov
A. V. Vishnevskii Surgery Institute
Academy of Medical Sciences of the USSR
Moscow, USSR
Translated from Russian by
Basil Haigh
Translation editor
F. A. Dodge, Jr.
IBM Thomas J. Watson Research Center
Yorktown Heights, New York
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Khodorov, Boris Izrailevich.
The problem of excitability.
Translation of Problema vozbudimosti.
Bibliography: p. 309-324.
1. Excitation. (Physiology) 2. Electrophysiology. 3. Cells-Permeability. I. Title.
QP341.K4913 591.1 '88 72-90339
ISBN-13:978-1-4613-4489-6 e-ISBN-13:978-1-4613-4487-2
DOl: 10.1007/978-1-4613-4487-2
The original Russian text, published by Meditsina Press in Leningrad in 1969, has
been corrected by the author for the present edition. This translation is published
under an agreement with Mezhdunarodnaya Kniga, the Soviet book export agency.
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PROBLEMA VOZBUDIMOSTI
Electricheskaya Vozbudimost' i Ionnaya Pronitsaemost' Kletochnoi Membrany
B. I. Khodorov
© 1974 Plenum Press, New York
Softcover reprint of the hardcover 1st edition 1974
A Division of Plenum Publishing Corporation
227 West 17th Street, New York, N.Y. 10011
United Kingdom edition published by Plenum Press, London
A Division of Plenum Publishing Company, Ltd.
4a Lower John Street, London WIR 3PD, England
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, microiilming,
recording, or otherwise, without written permission from the Publisher
In memory of my parents
s.
B. Piastro and I. G. Khodorov
Foreword
The Russian edition of this book appeared in 1969 and im
mediately gained widespread recognition as a reference work for
research workers interested in the physiology, biophysics, and
pharmacology of excitable tissues. There are several reasons
for the book's success.
It deals with a key problem in biology which has recently
been the subject of very intensive study and it is of great interest
to a wide scientific audience. Not only the fundamentals of the
modern membrane theory of biopotentials, but also the vast factual
material collected in the last decades by the study of the biophysical
and pharmacological properties of the ionic permeability pores of
the cell membrane, are described in the book in an authoritative
yet readable form. Special attention is paid in the book to the
systematic analysis of the consequences of the Hodgkin-Huxley
mathematical theory of the nervous impulse for the problem of
excitability. The relationship between the various parameters of
excitability (threshold potential, threshold current, useful time),
accommodation, and the action potential on the one hand, and the
constants of ionic permeability of the nerve fiber membrane, on the
other hand, is subjected to detailed examination in this context. To
do this, the author has made extensive use not only of experimental
results obtained on isolated fibers (especially single nodes of Ran
vier), but also the results of his own investigations on mathematical
models of excitable membranes. A chapter which deserves particular
attention is that which deals with the analysis of the effect of the
cable properties and geometry of excitable structures on the gen-
vii
viii FOREWORD
eration and conduction of the nervous impulse. In this section the
author also makes extensive use of material obtained on math
ematical models of nerve fibers. In the last chapter of the book a
critical analysis is made of modern views on the molecular mech
anisms of changes in ionic permeability of excitable membranes
and results obtained in the study of this problem by experiments
on artificial membranes are described. For this reason, although
several excellent books devoted to modern ideas of mechanisms
of activity of nerve fibers and cells exist, B. I. Khodorov's monograph
in no way repeats them.
By comparison with the original Russian edition, the book
has been substantially updated with new material obtained in the
period 1969-1971. The additions to Chapter VIII, dealing with the
analysis of mechanisms of rhythm transformation in geometrically
and (or) functionally heterogeneous nerve conductors will be of
great interest from this point of view; the reader will find infor
mation on the conduction of nervous impulses from a myelinated
axon into an unmyelinated terminal and also on the mechanisms
of automatic stabilization of the parameters of the membrane and
spreading action potential.
Besides summarizing the results obtained by the author and
his collaborators during many years of research, the book also
gives an excellent survey of research on electrically excitable
membranes. These features combine to make the book a valuable
aid to scientists in many different specialties concerned with the
problem of excitability.
I hope that the appearance of this English edition of B. I.
Khodorov's book will lead to the broadening of contacts between
Soviet and Western scientists conducting research in the field of the
general physiology of excitable membranes.
o. B. II'inskii
Preface
Excitability is the property of cell membranes to respond by
specific changes in ionic permeability and membrane potential to
the action of adequate stimuli.
By the character of their electrical response to stimulation,
excitable membranes can be conventionally divided into membranes
with a regenerative and membranes with a nonregenerative form of
electrogenesis.
Regenerative responses are characteristic of electrically ex
citable membranes. In these membranes there is a mutual inter
action between potential and ionic permeability: changes of poten
tial due to an electrical (or a chemical, thermal, or mechanical)
stimulus evoke changes in ionic permeability and ionic currents,
and these in turn strengthen or, under certain conditions, weaken
the original changes in membrane potential.
Generation of action potentials in nerve cells and nerve and
muscle fibers of invertebrates and vertebrates is based on this
reciprocal mechanism (Hodgkin, 1964b).
The course of electrogenesis is different in electrically in
excitable membranes, which include most postsynaptic membranes
and the membranes of receptor endings and secretory cells. In
these membranes, the connection between ionic permeability and
potential is purely in one way: an increase in permeability in
duced by a stimulus (a transmitter, for example) leads to changes
in membrane potential which, however, have no reCiprocal effect
on ionic permeability. For this reason the responses of elec-
ix
x PREFACE
trically inexcitable membranes (generator potentials in recep
tors, excitatory and inhibitory potentials in postsynaptic mem
branes) cannot become regenerative in character and always ex
hibit a continuously graded dependence on the strength of the sti
mu1us.
These differences in the relationships between membrane
potential and ionic permeability in electrically excitable and elec
trically inexcitable membranes can be represented schematically
as follows:
Electrically excitable membrane Electrically inexcitable membrane
Stimulus _ Change of potential Stimulus
1
(electric current) (transmitter)
l
,
Change in ionic Change in ionic
permeability permeability
l
Change in ionic currents Change in ionic currents
!
Change of potential
Several different types of active responses can be generated
by electrically excitable membranes: local responses, graded ac
tion potentials, action potentials obeying the "all or nothing" ru1e,
and hyperpolarization responses (see the survey by Grundfest,
1964).
A special place among these responses, because of its func
tional importance, is occupied by the nondecrementally propagating
action potential, for it is responsible for the most rapid and per
fect method of transmission of information in the mu1ticellu1ar or
ganism.
Under natural conditions, the stimu1us evoking generation of
the action potential in a nerve or muscle fiber is the local current
between the active (depolarized) and resting areas of the excitable
membrane. Accordingly, the study of the principles and mechanism
of action of the electric current on excitable structures has for
many years been a subject for special attention on the part of in
vestigators of many different schools and disciplines.
PREFACE xi
Particular progress has been made in the study of this prob
lem during the last two decades as the result of advances made in
cell physiology through the development and application of new
techniques for use in the study of the structure (electron micros
copy, x-ray structural analysis, chemical methods) and function
(intracellular microelectrodes, the voltage clamp, internal per
fusion of fibers, radioactive ions, and so on) of excitable mem
branes.
An important step in the development of the modern mem
brane theory of biopotentials (Hodgkin, Huxley, and Katz, 1949;
Hodgkin, 1964b) was the quantitative deSCription of the relation
ships between membrane potential, ionic permeability, and ionic
currents in the membranes of nerve fibers. Mathematical models
proposed for the membrane of the squid giant axon (Hodgkin and
Huxley, 1952d) and of the single node of Ranvier (Frankenhaeuser
and Huxley, 1964) not only enabled qualitative (intuitive) ideas on
mechanisms of formation of the nervous impulse to be verified,
but also enabled important conclusions to be drawn regarding the
relationships between individual constants of ionic permeability
of the membrane and parameters of excitability (threshold poten
tial, threshold current, utilization time), of accommodation, and
of the action potential.
The use of mathematical models also provided investigators
with new approaches to the study of the influence of the cable prop
erties of excitable structures on generation of the spreading action
potential. Attention was particularly concentrated on the quanti
tative analysis of the electrical behavior of excitable tissues with
complex geometry, such as the syncytia of cardiac or smooth
muscle, or branching dendrites.
Detailed studies of the kinetics of ionic permeability and ion
ic currents during action potential generation have not yet identi
fied the molecular mechanisms of membrane processes, and for
this reason many investigations have been conducted on artificial
membranes to shed light on this problem. Those receiving most
attention at the present time are experiments on artificial phos
pholipid membranes, which under the influence of certain proteins
and antibiotics acquire the properties of selective ionic permea
bility and electrical excitability.
xii PREFACE
An attempt is made in this monograph to summarize the main
achievements of modern nerve cell physiology in the study of ex
citability.
The book includes the results of the author's own experimental
(on single nodes of Ranvier) and theoretical (on mathematical mod
els) investigations undertaken in conjunction with V. I. Belyaev,
M. L. Bykhovskii, S. Ya. Vilenkin, E. G. Vornovitskii, R. I. Gri
likhes, F. B. Gul'ko, A. D. Korotkov, E. M. Peganov, and E. N.
Timin. Without their willing and productive collaboration, this
book would never have been written.
Great help with the preparation of this monograph was given
by O. B. n'inskii, to whom fell the hard tasks of its reviewing and
scientific editing.
Valuable critical comments have been made by M. B. Ber
kenblit, M. S. Markin, Yu. A. Chizmadzhev, A. M. Shkrob, and E. N.
Timin.
The author is most grateful to Academician of the Academy
of Medical Sciences of the USSR A. A. Vishnevskii, Director of the
A. V. Vishnevskii Institute of Surgery, to his deputy, Professor
A. S. Kharnas, and to Professor L. L. Shik, Head of the Depart
ment of Physiology, whose interest and support helped to trans
form this book from an idea to a reality.
