The Molecular Properties and Evolution of Excitable Cells

260 Pages·1967·3.672 MB·English

by  C. J. Duncan and G.A. Kerkut (Auth.)

INTERNATIONAL SERIES OF MONOGRAPHS
IN PURE AND APPLIED BIOLOGY
Division: ZOOLOGY
GENERAL EDITOR: G.A.KERKUT
VOLUME 35
THE MOLECULAR PROPERTIES
AND EVOLUTION
OF EXCITABLE CELLS
The Molecular Properties
and Evolution
of Excitable Cells
BY
C. J. DUNCAN
Department of Zoology, the University
of Durham, Durham
P E R G A M ON PRESS
OXFORD · LONDON · EDINBURGH · NEW YORK
TORONTO · SYDNEY · PARIS · BRAUNSCHWEIG
Pergamon Press Ltd., Headington Hill Hall, Oxford
4 & 5 Fitzroy Square, London W.l
Pergamon Press (Scotland) Ltd., 2 & 3 Teviot Place, Edinburgh 1
Pergamon Press Inc., 44-01 21st Street, Long Island City, New York 11101
Pergamon of Canada, Ltd., 6 Adelaide Street East, Toronto, Ontario
Pergamon Press (Aust.) Pty. Ltd., 20-22 Margaret Street, Sydney, N.S.W.
Pergamon Press S.A.R.L., 24 rue des Écoles, Paris 5 e
Vieweg & Sohn GmbH, Burgplatz 1, Braunschweig
Copyright © 1967
Pergamon Press Ltd.
First edition 1967
Library of Congress Catalog Card No. 66-29718
2797/67
FOR
My Mother
My. Father and My Wife
PREFACE
OVER the past 5 years I have been interested in the manner in which
excitable cells such as nerves, muscles and sense organs operate.
I was therefore pleased when Dr. G. A. Kerkut suggested that I
should present these ideas in book form with the accent on the
theoretical aspects of the subject.
My main aim has been to present a concrete hypothesis, and for
this reason much of the experimental evidence is presented in sum-
mary form, although in certain instances further amplification can
be found in the figure legends.
I have redrawn many of the figures used, and the following jour-
nals, societies and publishers gave their permission to reproduce
material: Academic Press (Arch. Biochem. Biophys.), Acta Physio-
logica Scandinavica, American Physiological Society, Animal Be-
haviour, Annual Reviews Inc., Elsevier Publishing Company (Bio-
chim. Biophys. Acta, 3, p. 503, Fig. 4), Japanese Journal of Physio-
logy, Journal of Biological Chemistry, Journal of Physiology, Nature,
New York Academy of Sciences, the Rockefeller Institute Press (J.
gen. Physiol.), the Royal Society, the Society for Experimental
Biology, the Wistar Institute of Anatomy and Biology (J. cell. comp.
Physiol.), and Yale University Press.
I am most grateful to my friends (especially those at Liverpool,
where these ideas were first formulated) who have given generously
of their time and have helped me in many ways. In particular it is
a pleasure to thank Professor D. Barker, Dr. K. Bowler, Dr. G.A.
Kerkut, Professor R. J.Pumphrey, F.R.S., Dr. D. V. Roberts and
Dr. C.L.Smith. However, the responsibility for the errors and
shortcomings is mine alone.
I should like to thank Mrs. R. Bullen and Miss L. Rocks, who
helped me with much of the typing of the final manuscript, and I
am grateful to my wife who not only typed a great deal of the first
draft but also helped in the many tasks associated with checking
and preparing the manuscript for press.
xi
CHAPTER 1
INTRODUCTION
THE purpose of this monograph is to present evidence and to deve-
lop a hypothesis concerning the evolution and properties of ex-
citable cells. Such a story is essentially concerned with the proper-
ties of the bounding membrane of such cells and with its complex
permeability system, upon which the process of excitation depends.
As a review it is not comprehensive, because neurophysiologists are
fortunate in having many detailed accounts of axonal and synaptic
transmission, and in particular two recent monographs by A.L.
Hodgkin {The Conduction of the Nervous Impulse, 1964) and
J.C.Eccles {The Physiology of Synapses, 1964) give a summary of
current thinking in these fields. Apart from a brief paragraph of
introduction where necessary, I shall not attempt to duplicate their
approach; the reader is referred to the extensive bibliographies
which these books contain. Rather, I shall take the phenomena
described by Hodgkin and Eccles as a starting point and try to
present a hypothesis concerning the events which underlie them,
assembling evidence from the results of a range of experimental
techniques and disciplines. Again, it would be almost impossible to
cover all the relevant literature in the fields of electron microscopy,
histochemistry, biochemistry, physiology, pharmacology and mole-
cular biology, and I have relied on quoting reviews where possible
or selecting what seems to me to be suitable experimental evidence
to support each hypothesis. The result is not an exhaustive review,
but a monograph with a strong personal flavour, in which I shall
try to suggest the ways in which excitable cells operate. The primary
aim will be one of unification, a presentation of uniform concepts
from the wealth of data available from active fields of research. It
will be suggested that excitable cells could have evolved from a
primitive condition which is illustrated in such simple animals as
Amoeba, the hypothesis presented in this monograph having been
developed from some preliminary ideas concerning the properties
1
2 MOLECULAR PROPERTIES AND EVOLUTION
of excitable cells which have been given in previous papers (Duncan,
1963a, 1964a, 1965).
The complex process of nervous conduction is, of course, as-
sociated with the subtle ionic permeability properties of the nerve
membrane, their transient transformation during the passage of the
action potential and the maintenance of the differential ionic con-
centration across the nerve membrane by the action of the active
cation pump. In this review, therefore, we shall consider evidence
concerning the nature of the system which controls the passive
ionic permeability of the membrane of the excitable cell and suggest
how it may have originated, evolved and differentiated.
The membrane theory of conduction along the nerve fibre may be
stated briefly as follows. The membrane is assumed to be more
permeable to potassium than to sodium ions in the resting condi-
tion. If the membrane were permeable to potassium ions only, the
potential difference across it would approach the maximum value
predicted by the Nernst equation :
[K]o
VK = — · l0g
Γ e [K]
t
[Na]
0
Γ [Na]
t
INTRODUCTION 3
would be + 55 mV for a squid giant axon, giving a theoretical total
potential change of 130 mV. Again, recorded values for the positive
overshoot fall below the predicted maximum, indicating that the
membrane is not completely selective for sodium.
FIG. 1.1. Diagram to illustrate the membrane theory of axonal conduc-
tion. The potentials across the membrane of the squid axon are shown
under conditions of excitation and rest, together with their approximate
derivation from the Nernst equation.
Propagation of the action potential is achieved by a flow of cur-
rent in a local circuit between the active area and the resting region of
the nerve membrane immediately ahead. The current flow reduces
the membrane potential in the inactive region, and this depolariza-
tion in turn causes a rise in sodium permeability there (see Chap-
ter 10). Experimental evidence suggests that an active cation pump
is also present in the membrane and serves to drive out ions against
their concentration gradient, the ions having been accumulated
either during nerve activity or by membrane leakage. There is good
evidence (Chapter 4) that a membrane adenosine triophosphatase
(ATPase) enzyme system is concerned with such transport and that it
is dependent on metabolism and a supply of ATP (see review, Hodg-
kin, 1964).
4 MOLECULAR PROPERTIES AND EVOLUTION
1. THE ORGANIZATION OF EXCITABLE CELLS
Grundfest (1957, 1959a, b, 1961) has elaborated on the early
ideas of Parker (1919) and has produced a hypothesis for the evo-
lution and organization of excitable cells. Parker (1919) suggested
that the nervous system of the Metazoa evolved from a cell which
was a primitive receptor-effector. Such a cell is found in sponges;
it is sensitive to stimuli and is able to respond by appropriate ac-
tivity. The receptor and effector components became separated in
space, and specialized for their separate functions during the evolu-
tion of the Metazoa. Connection between the two was maintained
by the development of an axonal component in the receptor, and
distinct neuronal cells with integrative functions were subsequently
evolved.
Input Conductile component Output
component Γ1" component
Ί
Graded,
Specific localized de- Graded
stimuli or secretion '
hyperpolarization
Excitation Depolarizing
. Inhibition t All-sopri-kneost hing Hyperpolarizing
FIG. 1.2. Scheme suggested by Grundfest (1957, 1959a, b, 1961) for the
organization of excitable cells. There are three components of action,
namely input, conduction and output (upper part of figure). The lower
part of the figure illustrates the types of potential changes which are re-
corded and also indicates that the secretion of the output may have either
a depolarizing (excitatory) or hyperpolarizing (inhibitory) action.
Grundfest (1957, 1959a) has shown, however, that although such
evolutionary specialization has taken place, each excitable cell has
retained its dual role of receptor and effector and has, therefore,
three components of action, namely input, conductile and output
portions. Grundfest's scheme is summarized in Fig. 1.2.
(i) The input component is not electrically excitable, but responds
INTRODUCTION 5
to specific stimuli and is chemosensitive (see Chapter 7). Thus, an
input area may be a sensory ending, sensitive to certain stimulus
energies, or a postsynaptic membrane which is excited by its trans-
mitter chemical. All input components, therefore, act as transducers,
converting the stimulus energy into a localized, non-propagated,
electrical response. The stimulus may have either an excitatory or
an inhibitory effect, producing either a depolarization or a hyper-
polarization respectively. The essential features of these localized
changes in resting potential are that they are maintained and graded,
and appropriate depolarization is able to initiate a train of spike
potentials in the conducting portion of the excitable cell.
(ii) The conductile component has the converse properties. It is not
chemosensitive, but responds to electrical stimulation. As stated
above, the sodium-permeability properties of the axon are sensitive
to depolarization. The electrical response of the conductile cell, far
from being graded, is the all-or-none spike potential. A definite
threshold intensity is required to stimulate the axon, but above this
level, and with other factors constant, the size and shape of the spike
potential is independent of the intensity of the stimulus. Unlike the
potentials recorded at input components, the spike potentials are
propagated (see above).
(iii) The output component. The arrival of the spike potentials at
the effector-output component initiates secretory activity and the
liberation of the chemical transmitter which is then able to act upon
the input component of the next excitable cell in the neuronal chain.
It is Grundfest's hypothesis that all excitable cells can be fitted
within this generalized scheme.
Some confusion exists in the terminology that has been proposed
for the localized potentials developed at input components. In this
review, the terminology proposed by Davis (1961) for sense organs
will be followed (Pringle, 1962) and is shown in simplified form in
Fig. 1.3. Not all features shown in the diagram are present in all
sense organs (e.g. accessory structures). The generator potential is
defined as that potential which triggers the all-or-none response of
the initial segment of the sensory neuron, whilst the receptor poten-
tial is defined in terms of the response of the sense organ to the
action of the external energy. There may be no specialized receptor
cell, the response being developed in the sensory neuron or, alter-
natively, there may be no synapse with a chemical mediator, the
potential in the receptor cell stimulating the initial segment directly
EMP 2