The Journal of Physiology, Vol. 243, No. 1 Frontispiece: Huxley

The Journal of Physiology, Vol. 243, No.
1 Frontispiece
eI
sT
'A
./
or
.s
> j
r j __
A. F. HUXLEY
J. Physiol. (1974), 243, pp. 1-43 1
With 1 plate and 12 text-figure8
Printed in Great Britain
REVIEW LECTURE
MUSCULAR CONTRACTION
GIVEN AT THE MEETING OF THE PHYSIOLOGICAL SOCIETY AT
LEEDS UNIVERSITY ON 14--15 DECEMBER 1973
BY A. F. HUXLEY
From the Department of Physiology,
University College London, Gower Street, London WC1E 6BT
INTRODUCTION
It is a particular pleasure to me that this Review Lecture is being held
in the university where the late Professor W. T. Astbury worked. He was
among the first to investigate muscles by means of X-ray diffraction, and
his successes and his enthusiasm prepared the way for this technique to
become the most powerful method for investigating the submicroscopic
structure of living muscle and its changes during physiological activity.
In this lecture, I shall mainly be going over the development, during the
last 20 years, of ideas about the origin of the force produced by striated
muscle. In the same period there have also been great advances in other
aspects of muscle physiology, and by way of introduction I will first run
over the steps that are now believed to lead up to the contractile process
itself. Throughout, I shall confine myself to the twitch fibres of striated
muscle of amphibians and mammals, and I shall concentrate on experi-
ments with living muscle, especially those on isolated fibres. Structural
and biochemical investigations have been at least equally productive,
but I am not able to do justice to these aspects, and in any case, the
physiological side provides more than enough material for a single lecture.
Activation of the contractile material

Excitation. An action potential in an individual muscle fibre is set up at
any point where the internal potential is raised by some 40 mV above its
resting level (about -90 mV relative to the surrounding fluid). This may
occur either at the end-plate (when stimulation is through the motor nerve
fibre) or opposite the cathode if direct stimulation is employed. The action
potential propagates in both directions to the ends of the fibre, by a
mechanism which differs only in details from that which operates in nerve
fibres (Hodgkin, 1951).
I -2
2 A. F. HUXLEY
It is the change of membrane potential itself (not, for example, any
associated longitudinal current in the interior of the fibre) that is effective
in causing the fibre contents to contract (Kuffler, 1946). The relation
between membrane potential change and mechanical response is graded
(apart from the phenomena mentioned in the next section), and the all-
or-none character of the twitch is a consequence of the all-or-none
character of the electrical change at the surface membrane (E. D. Adrian,
1922; Gelfan, 1931, 1933).
Inward spread. As well as propagating along the surface membrane,
however, this potential change also spreads inwards along the mem-
branes of the tubules, invaginated from the surface membrane, which
constitute the 'T' (transverse) system. These tubules run in the spaces
between the myofibrils, forming transverse networks across the fibre at
definite positions in the striation pattern, and they are open to the
extracellular space (Endo, 1964, 1966; H. E. Huxley, 1964a; Page, 1964;
D. K. Hill, 1964; Franzini-Armstrong & Porter, 1964), although their
openings have seldom been clearly seen in electron micrographs of mammal-
ian or adult amphibian muscle. In amphibians there is one transverse
network per sarcomere, at the level of the Z line, while in mammals there
are two per sarcomere, one near each boundary between A and I bands;
in a bird, both of these patterns have been seen in different muscles (Page,
1969).
If the lumen of one of these networks is made electrically negative by
applying an electrical pulse to a micropipette in contact with the surface
of the fibre over one of the openings, a highly localized contraction occurs,
spreading inwards for a substantial distance but confined to a single I
band in muscles whose transverse tubules are at the level of the Z line
(A. F. Huxley & R. E. Taylor, 1955, 1958), or to a single half-sarcomere
if there are two sets of tubules per sarcomere (A. F. Huxley & R. W.
Straub, 1958). The electrical conduction in the transverse tubules has
recently been shown to be a regenerative process (Costantin, 1970;
Costantin & S. R. Taylor, 1971), similar to the longitudinal propagation
along the surface membrane but with much lower safety factor (R. H.
Adrian & Peachey, 1973), and this accounts for the remarkable speed with
which the onset of shortening spreads inwards within each fibre (Gonzalez-
Serratos, 1971).
In the local-stimulation experiments with a small-diameter pipette,
one of these two-dimensional networks is being stimulated through a
single tubule connecting to the outside of the fibre; this situation is un-
favourable for propagation and, together with the low safety-factor for
propagation when the network is simultaneously stimulated at all of its
connexions to the outside, probably accounts for the fact that the
MUSCULAR CONTRACTION 3
response did not spread inwards beyond 10 Iam or so. With larger pipettes,
Strickholm (1962, 1966) did sometimes obtain responses in which several
sarcomeres contracted over the whole cross-section of an isolated fibre,
and the graded local contractions obtained by Gelfan (1933) in response
to a long-lasting positive potential applied through a pipette of 15 /tm
diameter contained an initial twitch-like component. There is no explana-
tion yet for the remarkable responses recorded by Sugi & Ochi (1967),
in which a ring-shaped contraction encircling the fibre took place when a
rather strong negative pulse was applied to a pipette in contact with the
fibre surface.
Intracellular calcium release. For much of their length, these transverse
tubules are flanked on both sides by vesicles belonging to the sarcoplasmic
reticulum, known as the lateral cisternae. The membrane potential change
in the tubules of the T system somehow causes calcium ions to be liber-
ated from the lateral cisternae; the mechanism is not known but small
membrane currents probably associated with this 'gating' process have
recently been described (Schneider & Chandler, 1973). The release of
calcium ions was first inferred from indirect evidence, but has now been
demonstrated by two elegant direct methods. Jdbsis & O'Connor (1966)
succeeded in getting the calcium-sensitive dye, murexide, to enter the
cells of toad muscle through their surface membrane, and recorded changes
of light absorption that indicated a transient rise in intracellular calcium
concentration when the muscle was stimulated. The second method makes
use of aequorin, a protein isolated from a jellyfish, Aequorea (Shimomura,
Johnson & Saiga, 1962), which luminesces when exposed to calcium ions
even at concentrations of the order of 10-6 M. A solution of aequorin is
injected into a muscle fibre, and when the fibre is stimulated an emission
of light occurs. This experiment was first performed by Ridgway & Ashley
(1967; Ashley & Ridgway, 1970) in the very large muscle fibres of a
barnacle, and the remarkable feat of doing the same thing in an isolated
frog muscle fibre was reported to the Society earlier this year (Rudel &
S. R. Taylor, 1973). Both methods show that after a single stimulus the
free calcium concentration reaches its maximum early in the rising phase
of tension, and has dropped practically back to its resting level by the
time the tension reaches its peak.
These calcium ions diffuse into the interior of the myofibrils, where they
bring the contractile proteins into the active state by combining with the
regulatory protein 'troponin' (Ebashi, 1963; Ebashi & Kodama, 1965).
This protein, itself consisting of three separable components, is a consti-
tuent of the thin filaments, and appears to exert its control on the inter-
actions of myosin and actin through yet another component of the
thin filaments, the native form of the protein tropomyosin (Bailey, 1948).
4 A. F. HUXLEY
Relaxation is brought about by active transport of calcium into longi-
tudinal elements of the sarcoplasmic reticulum, lowering the free calcium
concentration so that calcium dissociates from the troponin, and the resting
state of the contractile material is restored.
The role of calcium in the regulation of contraction was very well
reviewed a few years ago by Ebashi and his colleagues (Ebashi & Endo,
1968; Ebashi, Endo & Ohtsuki, 1969).
THE MECHANISM OF CONTRACTION

The position in 1945-1953
The accepted background. By the end of the second world war, a large
body of knowledge of the biochemical and physiological aspects of muscu-
lar contraction had been built up. Dr Dorothy Needham's 'Machina
Carnis' (1971) provides a most valuable account of this, as well as of more
recent work, while the numerous contributions of A. V. Hill and his school
are beautifully reviewed in his 'Trails and Trials in Physiology' (1965).
Some of the most important points are summarized in the following
paragraphs; subsequent work has confirmed all of them, with quantitative
modifications in some respects. They still provide a background to all
theorizing about the processes which actually give rise to tension and
shortening.
A ATP is the link between metabolism and contraction in the sense
that (a) this substance is synthesized from ADP and inorganic phosphate
as a result of glycolytic and oxidative metabolism within each muscle
cell and (b) shortening of the muscle is coupled to the reconversion of
this substance to ADP+Pi. Phosphorylcreatine (PCr) acts as a buffer,
enabling relatively large quantities of ATP to be made available on a
short time scale by the Lohmann reaction:
ADP + PCr = ATP + creatine.
B 'Myosin' (Ktihne, 1864) is itself an ATPase (Engelhardt & Lyubi-
mova, 1939).
C The physical properties of myosin threads (Engelhardt, Lyubimova &
Meitina, 1941) and of myosin in solution (Needham, Shen, Needham &
Lawrence, 1941; Dainty et al. 1944) are drastically altered when ATP is
present.
D KUhne's 'myosin' can be separated into two proteins, 'actin', and
what is now known as myosin (F. B. Straub, 1943). In this separation,
the proteins are dissociated from a complex, 'actomyosin', by the action
of ATP (A. Szent-Gybrgyi, 1943).
E When a muscle is fully activated by tetanic stimulation, it will
1-4
1-2
1 *0'
08
0
C-
06
04
02
02 04 06 08 1-0
V/Vmax
Text-fig. 1. Force-velocity relation. The degree of curvature of the relation
varies between different preparations, and with temperature. Continuous
line: Hill's (1938) relation,
P/PO = (1-VVIV.)I(l + (PO/a) VIV..),
with P./a = 4, appropriate for frog muscle at 0° C.
This equation is a good fit to observations at loads below P0 (shortening).
In lengthening, Katz (1939) found the relation shown as a dotted line; in
addition there is 'give' which is limited in extent when P is only a little
greater than P0 but becomes very rapid and extensive as P approaches
1-8 P0 approx.
Crosses: Fenn & Marsh's (1935) relation, P = Woe aV-kV, with
WO = 0*95P0, a = 3.4/VI,, k = 0-03 P0/V., chosen to fit the continuous
line as well as possible. In their curve-fitting, Fenn & Marsh did not make
use of a measured P0.
Circles: values calculated from the theory of A. F. Huxley (1957).
6 A. F. HUXLEY
shorten at a speed which is a definite function of the load applied to
it (Fenn & Marsh, 1935). A. V. Hill (1938) showed that to a sufficient
degree of approximation, this function is part of a rectangular hyperbola
(Text-fig. 1).
F When a load greater than the isometric tetanus tension (PO) is
applied to a stimulated muscle, the steady speed of lengthening is much
smaller than would be expected from an extrapolation from speeds of
shortening at loads below P0 (Hill, 1938; Katz, 1939; Text-fig. 1). In
addition, the muscle 'gives' when the load is first applied; the extent of
this 'give' is small when the load is only a little greater than P0 but be-
comes very large, simulating complete relaxation, as the load approaches
a value of approximately 1-8 P0 (Katz, 1939).
025
Hill (1938)
Total
0.20
extra energy
Hill (1964) liberation
> 0110
C
0 05 M mechanical
g S~~~~~~~ower
0 0.2 0.4 0.6 0-8 1.0

VIVmax,
Text-fig. 2. Rate of energy liberation as a function of shortening speed,
during steady shortening in a tetanic contraction. Lower curve: rate of
doing external work, calculated from Hill's (1938) force-velocity relation
(Fig. 1). Upper curves: rate of appearance of heat plus work, in excess of the
rate of appearance of heat in an isometric contraction. The latter is about
0-06 PoV,,,X.
The extra energy liberated per unit change of length is equal to the
slope of the line joining the origin to the appropriate point on one of the
upper curves.
G The liberation of energy in the form of work plus heat (presumably

proportional to the utilization of substrate by the biochemical processes
coupled to contraction) is greater when a muscle is allowed to shorten
and do work than when it is held isometric (Fenn, 1923, 1924).
H This increase in the rate of energy liberation flattens off at higher
speeds of shortening (A. V. Hill, 1938; Text-fig. 2), i.e. the energy liberated
per unit change of length becomes less as the speed of shortening is
increased.
I During forced lengthening, the rate of energy liberation (heat produced
minus work done on the muscle) is much less than the rate during iso-
metric contraction (Fenn, 1924; Hill, 1938; Aubert, 1944a, b, 1948).
J The wide-angle X-ray diffraction picture is not very different in active
muscle from what it is in relaxed muscle (Astbury, 1947).
100
SP
C.
0
0 50
a ~~~~~~~~A4
0 Length (%/) 50 100 150 200
01.00 2-00 3-00 4-0

Text-fig. 3. Length-tension relation in isolated frog muscle fibres. Ordinate:
isometric tetanus tension developed (total tension during tetanus minus
resting tension); percent of maximum. Points: from Ramsey & Street
(1940). Length expressed as percentage of slack length, which was also the
length where developed tension was a maximum.
Continuous lines: length-tension relation found by Gordon et al. (1966 b).
Lower abscissa scale gives striation spacing in micrometres. Drawn so that
2-05 ,um striation spacing, the average slack length, corresponds to 100 %
on Ramsey & Street's length scale. The differences from Ramsey &
Street's results are due to: (a) above optimum length, non-uniformity of
striation spacing gives an exaggerated tension except when the 'spot-
follower' of Gordon et al. is used, and (b) at very short lengths, Ramsey &
Street's points are from very long-lasting contractions, and the fibres had
gone into the irreversible 'delta state'.
Diagrams show critical stages in the degree of overlap of the filaments,
as in Text-fig. 5. At all striation spacings above about 2-0 /tm, the developed
tension found by Gordon et al. is closely proportional to the number of
thick-filament projections overlapped by thin filaments.
K The isometric tension developed by muscle when tetanically stimu-

lated depends in a characteristic way on the length at which it is held,
declining steeply on either side of an optimum which is close to the slack
length (Ramsey & Street, 1940; Text-fig. 3).
8 A. F. HUXLEY
Confirmation of these points. The evidence quoted in the last section all
dates from before 1945. Among more recent papers which confirm and
extend the conclusions are the following:
A The role of ATP was originally postulated on very indirect evidence.
Conversion of ATP to ADP during contraction could not be demonstrated
experimentally (except in extreme fatigue), but this was attributed to
rapid re-synthesis of the ATP by transphosphorylation from phosphoryl-
creatine. Since the war, utilization of ATP has been repeatedly demon-
strated in preparations where the contractile material is directly exposed
to an artificial medium (glycerinated fibres; fragmented myofibrils; the
stripped- or skinned-fibre preparation of Natori; see books by Weber
(1958) and Arronet (1973)). Direct evidence of ATP utilization in excitable,
intact muscle was at last obtained by Cain, Infante & Davies (1962), who
used fluorodinitrobenzene as an inhibitor of creatine phosphokinase to
prevent the rephosphorylation of the ADP that was formed.
B There is now an enormous literature on the ATPase activity of myosin,
of proteolytic fragments of myosin, and of actomyosin. A recent review is
that of E. W. Taylor (1972).
C and D The kinetics of the dissociation of actomyosin through inter-
action with ATP have been investigated with rapid-reaction techniques
by several groups (Tonomura & Watanabe, 1952; Barany, Edman &
Palis, 1952; Tonomura, 1972; Mommaerts, 1956; Lymn & Taylor, 1971).
G and H Energy liberation as a function of shortening speed has been
further investigated by Hill (1949a, b, 1964), using measurements of the
rate of production of heat and of doing work. There has been controversy
whether 'shortening heat' appears as a term in the total energy liberated
in a cycle of contraction and relaxation, or whether it might be a reflexion
of some process that is reversed during relaxation. It is now seems clear
that much, but not all, of 'shortening heat' does appear as a contribution
to the total energy liberated (Aubert & Lebacq, 1971; Dickinson &
Woledge, 1973).
Hill (1964) showed that the rate of energy liberation falls off more
sharply with increase of shortening speed than indicated in his 1938 paper;
indeed, the rate passes through a maximum when the speed of shortening
is about 0-6 Vmax (Text-fig. 2).
The energy which appears as heat is far from being accounted for by
the measured changes in ATP and PCr concentrations in the muscle
during the contraction (Kushmerick, Larson & Davies, 1969; Gilbert,
Kretzschmar, Wilkie & Woledge, 1971).
I The drastic fall in energy liberation when a muscle is stretched during
contraction has been repeatedly confirmed both by myothermal methods
(Abbott, Aubert & Hill, 1951; Abbott & Aubert, 1951; Hill & Howarth,
1959; Wilkie, 1968) and by measurement of phosphorylcreatine utilization
(Wilkie, 1968) and appearance of inorganic phosphate (Curtin & Davies,
1973). It is not yet clear whether the net energy liberation in a complete
twitch can drop to zero, as suggested by the results of Hill & Howarth
(1959) or whether there is always a residual energy liberation at least
equal to the 'activation heat'. The former would require that the energy-
yielding reactions associated with the activation process can actually be
reversed by stretch during the contraction; the latter would only require
that stretching suppresses the ATP splitting by the contractile proteins.
J Interest in X-ray diffraction studies of muscle has switched from the
wide-angle pattern (related to spacings of less than 1 nm) to the low-angle
pattern (related to spacings of 5-50 nm). H. E. Huxley has been the
chief pioneer in this work (see, for example, H. E. Huxley (1953a) and
H. E. Huxley & Brown (1967)). An excellent review was published in 1968
by Professor Jean Hanson, whose death this summer was a severe and
unexpected blow to her many friends, and also to the progress of research
on muscle. Much of the more recent X-ray work is reviewed in the articles
in the section entitled 'Muscle Structure' in the volume produced from
the 1972 Cold Spring Harbor Symposium (vol. 37, 1973). Many significant
changes in the diffraction pattern have been found, but the absence of
any suggestion of major change in the backbone structure of the filaments
has been confirmed throughout.
K The length-tension curve was re-investigated by Gordon, A. F. Huxley
& Julian (1966b), who confirmed the main features reported by Ramsey &
Street (1940) but eliminated an error due to the non-uniformity of muscle
fibres when they are greatly stretched (see p. 17).
Continuous-filament theories. For many years, it had been generally
supposed that the contractile material was in the form of continuous
filaments that shortened by some kind of folding or coiling. Points A-G
in the preceding paragraphs were readily assimilated into this framework
of ideas, and early electron microscope investigations of muscle structure
were claimed as confirming the existence of continuous filaments (Hall,
Jakus & Schmitt, 1946; Rozsa, Szent-Gy6rgyi & Wyckoff, 1950). During
the period 1945-1953 it was almost universally supposed that the sequence
of events in a contraction was as follows.
1. Actin and myosin exist as separate proteins in the resting muscle
fibre (cf. point D).
2. When the fibre is stimulated, the actin and myosin interact to form
continuous filaments of 'actomyosin'.
3. This actomyosin acts as an ATPase (point B), the action of the enzyme
including a step which causes or allows the length of the filament to be
reduced (point C).
10 A. F. HUXLEY
This theory left open many questions about the intimate nature of the
shortening process. Does the hydrolysis of ATP occur during the con-
traction itself, or is contraction a spontaneous process, the actin and
myosin being dissociated by ATP during relaxation? Does the tendency
to shorten arise from the formation of new bonds in the shortened state
('internal energy' theories: Meyer, 1929; Buchthal & Kaiser, 1951;
Polissar, 1952), or is it attributable to an increased freedom of the fila-
ments to coil up under the influence of thermal agitation ('entropy
theories': Wohlisch, 1940; Pryor, 1950; Morales & Botts, 1952)?
In so far as ATP splitting is coupled to shortening, continuous-filament
theories automatically account for point G. However, they provide no
basis for point H, i.e. chemical change per unit change of length is less
the higher the speed of shortening (Needham (1950) pointed out that this
feature might be explained by cyclic action of the contractile units within
a single contraction (see p. 20), but this idea is difficult to incorporate into
any continuous-filament theory). The very specific theory worked out by
Polissar (1952) accounted adequately for the force-velocity relation (point
E); he claimed to explain the rate of energy liberation (point H) but seems
to have mistaken A. V. Hill's 'shortening heat' for the total energy
liberated in the shortening (the work done is an additional element of
liberated energy). The absence of change in the X-ray diffraction pattern
(point I) could not be easily reconciled with the idea of folding of the
filaments.
Sliding filaments
The continuous-filament view of muscle was upset by three discoveries
made just 20 years ago.
1. The myosin is confined to the A bands, i.e. the bands with the higher
refractive index (Hasselbach, 1953; Hanson & H. E. Huxley, 1953).
2. The filament array seen with the electron microscope within each
myofibril consists of two interdigitating sets of filaments (H. E. Huxley,
1953b).
3. The length of the A bands does not alter when the muscle is
stretched or shortened (Harman, 1954; H. E. Huxley & Hanson, 1954;
A. F. Huxley & Niedergerke, 1954).
I shall not spend time either in discussing these experiments, as they
are well known and have been reviewed many times (e.g. Hanson &
H. E. Huxley, 1955; A. F. Huxley, 1957; H. E. Huxley, 1960), or in
reviewing the extent to which their results had been foreshadowed
in forgotten work by nineteenth century microscopists and chemists
(see A. F. Huxley, 1957). They led two of the groups of workers concerned
to the conclusion that length changes in striated muscle take place
by a relative sliding motion between two sets of filaments, each of
which retains a substantially unaltered length (H. E. Huxley, 1953b;
H. E. Huxley & Hanson, 1954; A. F. Huxley & Niedergerke, 1954). This is
represented in the familiar diagrams of Text-figs. 4 and 5. On the whole,
E
o
UIW
L
I1 b, 2 05 ,um
dii11
,llllllu 1 1111,,,,,, ,,,r I"1 ,.l,,, 1,1.11.11,
...,,....... .. ,H ,,,4 B........
1.|||1|||l111111111111Id lii .lll§11|1
Ill'Il~lW§|ll
I*- a, 1 60 Aim 01
005 jm
PM
1*- A band lIband -01 H zone -,
| ~ ~ ~~~I
I I I
Text-fig. 4. Relation of striation pattern to the double system of inter-

digitating filaments found by H. E. Huxley (1953b). The high refractive
index and the birefringence of the A bands are due to the thick filaments,
composed principally of myosin. The 'heavy meromyosin' part of each
myosin molecule projects, but a region at the middle of each thick filament is
free from these projections.
The thin filaments are principally composed of actin but contain also
the tropomyosin and the troponin. The H zone is recognized in fresh
material as a region in the middle of the A band with lower refractive index
than the outer parts. The diagram also shows the definitions of the dimen-
sions that are used in constructing Text-fig. 5.
Additional filaments, which are seen when the myosin is dissolved away
or when the muscle is stretched so far that there is a gap between the
thick and thin filaments (p. 14), are not shown because it is not yet known
where they attach to the other structures in the filament array. (From
Gordon et at. 1966b.)
this proposal was quickly accepted, and some observations which at first
seemed not to fit in with it have been satisfactorily explained. It is clearly
right to adopt it as a first approximation to what occurs when a muscle
changes its length; the following sections will discuss how far it can be
regarded as a complete account.
How nearly constant are the filament lengths? Although both light and
electron microscopy showed that the filament lengths stay approximately
constant, neither method would be capable of detecting changes of say a
few per cent if they were to occur either during passive length changes
or when a muscle is activated. The resolving power of the light micro-
scope is not sufficient, and electron microscope preparations are subject
12 A. F. HUXLEY
to uncertain amounts of shrinkage. The best available measurements are
those made by low-angle X-ray diffraction: H. E. Huxley & W. Brown
(1967) found no detectable change (i.e. less than a few tenths of one per
cent) in the thin-filament spacings, but an increase of about 1 % in the
thick-filament spacings, when the pattern from a muscle in isometric
contraction is compared with one from resting muscle. The filaments
must, of course, be extensible in some degree, and even an extension
of as little as 01 % as a direct consequence of the isometric tension
3:65 ,um (a+b)
-. 2-20-2 25 /4m (b+c)-*-

... ... ... ...
- 2
-. 2 05 4um (b) -
i .......................
3
4 1 85-1-900m (b -c) -
1.65 uim (a+z)
105ma R
i (b+z)
6- M2
Text-fig. 5. Critical stages in the increase of filament overlap as a fibre

shortens. The symbols for the dimensions are defined in Text-fig. 4. The
striation spacings for each stage of shortening are calculated from the fol-
lowing values of the dimensions, all for frog muscle: Thick filament
length, a: 1-60 ,um (Page & H. E. Huxley, 1963). Length of thin filaments
and Z line, b: 2-05 ,um (Page & H. E. Huxley, 1963). Thickness of Z line,
z: 0 05 /tm. Region of thick filament free from projections, c: 0-15-0-20 #rm
(H. E. Huxley, 1963).
More recent work suggests that the thin filaments are somewhat shorter,
probably about 1-95 #rm (Page, 1968). (From Gordon et al. 1966 b.)
carried by the filaments would be appreciable when one is trying to

interpret the mechanical properties of active muscle (see Text-fig. 8).
There is no clear evidence about the significance of the increase in thick-
filament spacings. Possible interpretations are:
(1) stretch caused by the isometric tension;
(2) elongation related to the activation process, perhaps causing the
latency relaxation, and
(3) a change of position of the myosin heads (generally assumed to be
the actual scatterers on the thick filament) relative to the backbone of the
filament.
Events in extreme shortening. Frog striated muscle shortens readily
to a striation spacing of about 1X3 ,tm (Goydon, A. F. Huxley & Julian,
1966b), and in long-lasting contractions it will shorten to about 1 jtm
(Ramsey & Street, 1940), though in this case the shortening is not fully
reversible ('delta state'). The approximate filament lengths shown on
Text-fig. 5 make it clear that long before the spacing of 1-3 /tm is reached
something beyond the most straightforward sliding must occur: the thin
filaments will have met at the centre of the sarcomere, and the ends of
the thick filaments will have come into contact with the Z lines.
As regards the thin filaments, it was shown by electron microscopy
(H. E. Huxley, 1964b) that their ends slide past each other, giving a
region of 'double overlap' at the centre of the sarcomere (Text-fig. 5),
which accounts for the CM band which appears in the light microscope
when vertebrate striated muscle shortens actively (P1. 1). This band, as
well as the better known Cz contraction band, has been seen in fixed and
stained preparations (Jordan, 1934), in living isolated fibres (A. F. Huxley
& Niedergerke, 1954, 1958; A. F. Huxley & Gordon, 1962; Plate 1) and in
separated myofibrils (H. E. Huxley & Hanson, 1954).
On further shortening, after the Z lines reach the ends of the thick
filaments, the other contraction band (Cz) appears, as a region of high
protein concentration or strong staining centred on the position of the Z
line. As regards vertebrate muscle, no one has yet deciphered the tangled
mass of material that is seen at this position under the electron microscope.
In frog muscle, at any rate, contraction bands are formed only during
active shortening. Fibrils that are passively shortened below their slack
length, either by active shortening of another part of the cross-section
of the same fibre (A. F. Huxley & Gordon, 1962; P1. 1) or by longitudinal
compression of an isolated fibre set in gelatin (Gonzalez-Serratos, 1971),
are thrown into folds, and the sliding motion of filaments does not go
beyond (and may not even reach) the point where the thin filaments meet
at the centre of the sarcomere (L. M. Brown, Gonzalez-Serratos & A. F.
Huxley, 1970). On relaxation after active shortening below this length,
the fibrils re-extend themselves, either throwing the whole fibre into curves
(Ramsey & Street, 1940) or, if this is prevented by surrounding materials,
making the fibrils go wavy within the straight cylindrical outline of the
whole fibre (Gonzalez-Serratos, 1971). A whole muscle can remain short-
ened as regards its overall dimensions after relaxation, but a subsequent
contraction has a long latent period corresponding to the straightening
out of the fibrils before they can begin to exert tension (Gonzalez-Serratos,
1971).
14 A. F. HUXLEY
Other filamentous constituents. H. E. Huxley & Hanson (1954, 1957)
gave clear evidence that after the thick filaments had been dissolved
away, some continuous structure remained in the myofibril; filamentous
material has been seen with the electron microscope in this situation
(Walcott & Ridgway, 1967). When a muscle is so far stretched that there
is a gap between the ends of the thick and thin filaments, some filamentous
material is seen crossing the gap (Carlsen, Knappeis & Buchthal, 1961;
A. F. Huxley & Peachey, 1961; Sjbstrand, 1962; McNeill & Hoyle, 1967;
Hoyle, 1968). It is not yet clear what these additional filaments are
composed of, or where they attach to the main system of thick and thin
filaments. It is natural to suppose that they carry much or all of that
part of the resting tension which is attributable to the fibre contents;
this is substantial although the sarcolemma makes a large contribution
at high degrees of extension (Casella, 1950; Podolsky, 1964; Fields &
Faber, 1970; Rapoport, 1972).
In the fibrillar muscles of insects there are well defined connexions from
the ends of the thick filaments to the Z lines (Auber & Couteaux, 1963)
but there is no reason to think that vertebrate muscle contains similar
structures.
Cause of the sliding movement
Alternative possibilities. As I mentioned earlier, it was soon accepted
that the shortening of vertebrate striated muscle took place by a relative
sliding motion of two sets of interdigitating filaments. This was an essen-
tial step that had to be taken before a realistic theory of contraction
could be developed, but in itself the 'sliding-filament theory' is not a
theory of contraction. The question to which we want to find the answer
is, what makes the filaments slide? The position is analogous to that
which existed in 1950, when the question was, what causes the filaments
(assumed continuous) to fold?
There are many kinds of interaction between two sorts of filaments
that might lead to movement which increases their overlap. The following
are some of those which have actually been proposed.
(1) On activation. the end of the thin filament becomes attached to an
adjacent thick filament, and the part of the thin filament which is in the
overlap zone shortens (Podolsky, 1959).
(2) Some kind of 'vernier' action takes place between sites on the thick
and thin filaments whose spacings are slightly different (Spencer &
Worthington, 1960; H. E. Huxley, 1964b).
(3) One of the types of filament undergoes small cyclic changes of
length, the other type of filament being temporarily attached to it during
the shortening phase of each cycle (Hanson & H. E. Huxley, 1955,
pp. 254-5; H. E. Huxley, 1960, p. 475; Asakura, Taniguchi & Oosawa,
1963).
(4) Superthin (T) filaments, claimed to run continuously from Z to Z
between the well known actin and myosin filaments, shorten under the
influence of the ATPase activity of myosin and actin (McNeill & Hoyle,
1967; Hoyle, 1968).
(5) A lateral repulsive force is generated between the filaments (Elliott,
Rome & Spencer, 1970), or the Z disks expand laterally (Ullrick, 1967),
and the consequent expansion of the lattice is coupled to shortening in the
way that is actually observed (by low-angle X-ray diffraction) when intact
muscle changes its length.
(6) The filaments move so as to increase the number of sites at which
some chemical interaction between actin and myosin can exist (H. E.
Huxley & Hanson, 1954).
(7) Electric charges of opposite sign, distributed along the two types
of filament, generate a net longitudinal force tending to increase the
amount of overlap (Yu, Dowben & Kornacker, 1970).
(8) Sites of interaction between the two types of filament, each genera-
ting a force in the shortening direction, are distributed within each overlap
zone (A. F. Huxley & Niedergerke, 1954). Examples of widely different
theories within this general category are those of H. H. Weber (1956, 1958),
A. F. Huxley (1957), Tonomura et al. (1961), Davies (1963), H. E. Huxley
(1969), A. F. Huxley & Simmons (1971b) and McClare (1972).
The first of these classes of theories (folding of thin filaments in overlap
zone) has been excluded because electron microscopy shows that the ends
of the thin filaments move inwards, and may overlap each other at the
centre of the A band, during active contraction (H. E. Huxley, 1964b).
The theories under headings (2), (3) and (4) have not been developed
to the point of making quantitative predictions which can be tested
against measurements of tension, heat production etc., and in most of the
cases there is no direct evidence for the events proposed as the origin of the
force. For these reasons they are not generally in favour, although they
cannot be rigorously excluded.
Theories (5) which depend on lateral expansion as the primary event
are made unlikely by a recent observation by Matsubara & Elliott
(1972). They measured the lateral spacing between filaments in fibres
from which the sarcolemma had been removed, and found that the depend-
ence on sarcomere length that had long been known in intact muscle did
not occur. Since these skinned fibres are perfectly capable of contraction,
this makes it very improbable that lateral expansion is a causal link in the
chain of events between chemical reaction and shortening.
Maximization of number of interaction sites (6). The basis of this theory
16 A. F. HUXLEY
is that the potential energy of the system is decreased by a definite amount
(say /E) for each actin-myosin interaction that is formed. The number of
interaction sites per unit cross-sectional area in one sarcomere is propor-
tional to the length x of each overlap zone. Now x =a + m - s2, where
a = actin filament length (from Z line to its end), m = half myosin fila-
ment length, and s = sarcomere length. Hence the potential energy of the
system can be written as
E = EO-kxlAE
= EO-kLXE(a + m-s2).
The tension (per unit cross-section) generated by the tendency to move
so as to reduce the potential energy of the system is dE/ds, i.e. kAE/2.
This is independent of the amount of overlap, in contradiction to the
direct proportionality suggested by the length-tension curve of Ramsey
& Street (1940) (confirmed later by Gordon, A. F. Huxley & Julian,
1966b; Text-fig. 3).
An alternative way of reaching this result is as follows. Forces at inter-
action sites within the overlap zone will be as much in the lengthening as
in the shortening direction and will thus cancel out; it is only at the ends
that there is a net attractive force which acts in the shortening direction.
The situation at the ends is, to a first approximation, the same whether
there is much or little overlap, so the force would not be expected to depend
greatly on overlap.
A further disadvantage of this type of theory is that it does not account
for shortening beyond the stage where the whole of each thin filament
overlaps with thick filament. This occurs at a sarcomere length of 1-6 or
1-7 Mum, but, as mentioned on p. 13, an isolated frog muscle fibre shortens
actually down to a sarcomere length of 1-3 or even 1 0 /hm.
Yet another difficulty is that this type of theory leads to the expectation
that the net chemical change associated with shortening, and hence the
total energy released as heat and work, will simply be proportional to the
increase in number of interaction sites and hence to the amount of shorten-
ing. This is contrary to the observations of A. V. Hill (1938), mentioned
as point H, p. 7. The disagreement is even more striking if the comparison
is made with Hill's more recent measurements (Hill, 1964; Fig. 2).
Electrostatic theories (7). These may be regarded as a sub-class of the
type of theory (6) discussed in the previous section, and they suffer from
all three of the difficulties pointed out there - failure to explain (a) the
proportionality between tension and overlap, (b) the ability to shorten
beyond the length where overlap is complete, and (c) the decrease of energy
liberation per unit change of length, as the speed of shortening is increased.
Electrostatic theories, however, meet an additional difficulty in that
there is a high concentration of potassium ions within the muscle fibre,
which would be expected to act as gegenions, and thus to screen any fixed
negative charges on one of the filaments.
As regards the dependence of tension on sarcomere length, Yu et al.
(1970) did introduce an auxiliary assumption into their electrostatic
theory to make tension decline in proportion to overlap. I do not feel
satisfied by this way of dealing with the difficulty: the decrease of tension
with increasing stretch is a feature which gives rise to several unpleasant
types of instability, and one would not expect it unless it was a direct
consequence of some inescapable aspect of the contraction mechanism.
Independent force-generators. Theories that come under the heading
(8) have the immediate attraction that they lead to a direct proportion-
ality between generated tension and overlap. This was suggested by
Ramsey & Street's (1940) length-tension curve, as was pointed out by
A. F. Huxley & Niedergerke (1954). Ramsey & Street's curve, however,
does not fall to zero until the degree of stretch is substantially greater
than ought to be needed to bring overlap to zero (compare Text-figs. 3
and 5). This point was investigated by Peachey and myself (A. F. Huxley
& Peachey, 1961). We found a simple explanation for the discrepancy:
when these isolated fibres from frog muscle are stretched, the ends do not
elongate as much as the middle, so that a situation is reached where the
striation spacing is perhaps 3-8 Mum, with no overlap, for the main part of
the fibre length, but drops to perhaps 3 0 Mm or less at the ends, so that
there is appreciable overlap for the last few tenths of a millimetre of fibre
at each end. When the fibre is stimulated with the tendons held, these
end regions shorten, stretching the middle part and causing the tension
to rise. In isotonic contractions, however, we found that no shortening
occurred in the parts of the fibre that were sufficiently elongated to
eliminate overlap. Podolsky (1964) also found that the stripped-fibre
preparation of Natori does not shorten in response to applied calcium if
it is stretched so far that no overlap is to be expected.
This non-uniformity introduces serious difficulties into determinations
of the true isometric length-tension curve. We overcame these by using
a photo-electric servo device to keep constant the distance between two
markers, stuck on to an isolated fibre, which defined a part of the fibre
length within which the striation spacing was nearly uniform (Gordon,
A. F. Huxley & Julian, 1966a, b). With this apparatus we obtained iso-
metric tetanus tensions (Text-fig. 3) that were closely proportional to
-overlap calculated from (a) the filament lengths obtained by Page &
H. E. Huxley (1963) and (b) the distribution of projections on the thick
filaments (H. E. Huxley, 1957, 1963). The 'overlap' to which tension was
proportional was therefore the overlap of thin filaments with that part of
18 A. F. HUXLEY
the thick filaments which carries projections, confirming not only the idea
that the interaction sites act as independent force generators, but also the
suggestion of H. E. Huxley (1957) that the projections from the thick
filaments, or 'cross-bridges', actually are the interaction sites.
It now appears (Page, 1968) that the thin-filament length of 2-05 gm
given by Page & Huxley (1963) was too great, and that the true value
(for twitch fibres of frog muscle) is probably -about 1-95 ,tm. This means
that the fit between our tension measurements and the overlap calculated
from our striation spacings is not as good as it seemed at the time. The
point deserves re-investigation, although the discrepancy is not beyond the
range of possible errors due to non-uniformity etc., combined with
uncertainty in the thick-filament length.
Another feature of contraction due to independent force-generators
in the overlap zone is that the speed of shortening under zero load ought
to be independent of the amount of overlap: the speed of sliding that
reduces the net power output from any cross-bridge (and therefore its
contribution to tension) to zero will be the same however many other
cross-bridges are active in the same overlap zone. One aspect of this
would show up in comparisons between muscle types with different
sarcomere (and filament) lengths: a muscle with shorter sarcomeres has a
larger number of overlap zones per millimetre of fibre length, and should
therefore shorten more rapidly than a muscle with longer sarcomeres. A
relation of this kind has long been known (Jasper & Pezard, 1934; Atwood,
Hoyle & Smyth, 1965) in arthropods, where sarcomere lengths vary greatly
from one muscle to another, and Niedergerke and I (A. F. Huxley &
Niedergerke, 1954) pointed out that this observation was consistent with
the idea of independent force generators in each overlap zone. Among
vertebrates there is almost no variation of sarcomere length, so a compari-
son of this kind cannot be made, but we found (A. F. Huxley & Julian,
1964; Gordon et al. 1966b) that reducing the overlap by increasing the
initial length of an isolated frog muscle fibre had practically no effect on
the speed of active shortening under very light load.
The idea of independent force generators distributed over each overlap
zone therefore provides straightforward explanations for two striking
features of contraction: isometric tetanus tension proportional to overlap,
and speed of unloaded shortening independent of overlap. In my view,
these points are sufficient grounds for provisionally assuming that the
mechanism of force generation is of this kind.
It should be said that these simple effects of changing the amount of
overlap apply only in the range of lengths above the slack length of the
fibre. Below the slack length, both isometric tension and speed of un-
loaded shortening fall off steeply, and although some of the features of this
decline seemed to be related to the length of the filaments (Gordon et
al. 1966b), it is now clear that a failure of inward spread of activation is
at least part of the explanation (S. R. Taylor & RUdel, 1970; RUdel &
S. R. Taylor, 1971).
Nature of the force generators
If on this basis we accept the idea that the relative force between thick
and thin filaments is made up of contributions from independent force
generators distributed within each overlap zone, and that these force
generators are to be identified with the projections seen by H. E. Huxley
(1957, 1963) on the thick filaments, our next question is: how does each one
of them generate its force? Most of the ideas now current assume that the
cross-bridges operate by some cycle of straightforward chemical inter-
actions - formation and breakage of bonds of various kinds - between
myosin, actin and ATP. McClare (1971), however, claims that all such
theories contain hidden assumptions and are contrary to the second law
of thermodynamics. He therefore asserts (1972) that it is necessary to
suppose that force is generated by some direct quantum-mechanical
interaction between excited states in the parts of the filaments that are
undergoing relative motion. I am not impressed by his arguments against
orthodox chemical theories: for example, he claimed that a theory of
mine (A. F. Huxley, 1957) would lead to a very low overall efficiency but
his argument depends on postulating an unreasonably large effect of ATP
in changing the equilibrium between the attached and detached conditions
of a cross-bridge. There is at present no observation that suggests posi-
tively that muscle is operated by a 'molecular energy mechanism' such
as McClare proposes, and until there is some such evidence, it remains
profitable to follow up the possibilities of contraction mechanisms that
depend on chemical processes that are better understood.
The following are some points that are suggested by evidence that
already existed when sliding filaments were proposed.
(a) Cyclic action. Each cross-bridge is presumably part of a myosin
molecule, and the total length of a myosin molecule is around 0-2 ,tm
(Portzehl, 1950; Mommaerts, 1951; since confirmed by electron micro-
scopy: Rice, 1961; Zobel & Carlson, 1963; H. E. Huxley, 1963; Rowe,
1964). The extent of sliding that may occur in a single contraction may,
however, be as great as 1 4am. It is therefore unlikely that any one cross-
bridge can remain attached, and exerting force, throughout such a contrac-
tion, and the natural conclusion is that, even within a single contraction,
individual cross-bridges undergo cycles in which they attach, generate force,
and detach.
(b) Detachment is presumably brought about by interaction with ATP.
20 A. F. HUXLEY
Szent-Gy6rgyi (1943) and Straub (1943) had shown that myosin and actin
are dissociated from each other on addition of ATP (point D, p. 4),
and this action has recently been shown to be very rapid (Lymn &
E. W. Taylor, 1971). It is an open question whether detachment is the
only change brought about by ATP, or whether it also re-sets some
condition in the myosin molecule which enables it to generate force in
a subsequent cycle.
(c) To explain point G (p. 6; increased energy release when shortening
is permitted), it is necessary to suppose that detachment (and therefore
ATP utilization) is slow unless shortening occurs and the sliding move-
ment allows the cross-bridge to complete the working part of its stroke.
Theories which do not incorporate a feature of this kind (e.g. the theory of
Oplatka, 1972) lead to a rate of energy liberation which is greatest in the
isometric state, i.e. the reverse of the 'Fenn effect'.
(d) The rate constant for attachment of a free cross-bridge must be
assumed to be moderate (in relation to speed of shortening) in order to
explain point H (p. 7), i.e. as speed of shortening increases, the energy
liberated per unit change of length becomes smaller. With this assumption,
the general explanation offered by Needham (1950) will operate: at low
speeds of shortening, each cross-bridge will have time to attach to each
site on the thin filament that comes within range as the filaments slide
past each other, but at higher speeds of sliding the rate constant for
attachment becomes rate-limiting, and the cross-bridge will miss some of
its opportunities for undergoing a cycle of attachment to a thin-filament
site.
(e) To explain point I (reduced energy liberation during stretch), the
attachment process must be assumed reversible, without splitting of ATP,
if the cross-bridge is prevented from going through its working stroke.
At several points, these arguments depend on the assumption that the
measured rate of liberation of heat plus work at each instant is an indica-
tion of the rate of consumption of ATP and PCr. This has not been con-
firmed by direct measurements of the change in concentration of these
substances (Kushmerick et al. 1969; Gilbert et al. 1971), and the discrep-
ancy between thermal and chemical measurements has not yet been
resolved. Caution is therefore necessary in accepting theoretical schemes
(such as my own: A. F. Huxley, 1957) that are based on this assumption.
A. F. Huxley's 1957 theory

In 1954-55 I worked out a theory of contraction (A. F. Huxley, 1957;
Text-fig. 6) which incorporated the features listed in the last section.
Within this framework the structural and chemical assumptions were the
simplest I could think of that would cause contraction to occur. The
assumptions about rate constants for attachment and detachment of
cross-bridges (both dependent on the position of the cross-bridge on the
thick filament relative to the thin-filament site) were also of an elementary
kind. With appropriate values for these rate constants and for the stiffness
and range of action of the cross-bridges, this theory gave an adequate
fit both to the force-velocity curve and to the relations between load and
rate of energy liberation found by A. V. Hill (1938). (Deshcherevskii
(1968) has indeed shown that a closely related, though less complete,
Myosin
filament
ActinA
filament
Equilibrium position laxly
of M site - I I
Text-fig. 6. Mechanism of contraction proposed by A. F. Huxley (1957).

The 'side-piece' M, elastically connected to the thick filament, is assumed
capable of binding to sites A (only one shown) on the thin filament.
Attachment occurs spontaneously but may be reversible; detachment occurs
principally by a process which involves the hydrolysis of an ATP molecule.
Attachment is accelerated by an enzyme attached to the thick filament,
placed to the right of 0 and therefore effective only at moments when M
is displaced in this direction by Brownian motion. As soon as an attach-
ment is made, the elastic connexion exerts a force in the direction tending
to shorten the muscle. The detachment process (utilizing ATP) is accelerated
by another enzyme attached to the thick filament, placed to the left of 0.
Detachment therefore occurs rapidly after the sliding movement has brought
the AM complex to positions where the elastic connexion exerts a force
which resists shortening.
kinetic theory leads exactly to the algebraic expressions fitted by Hill

(1938) to his results.) I regard this as good grounds for thinking that the
general outline of the theory is correct - cross-bridges operating in a
cycle consisting of attachment with moderate rate constant, exertion
of force, and detachment with high rate constant after sliding motion of
the filaments sufficient to bring the force near to zero. The agreement with
experimental results would remain if these kinetic features were retained
but the structural and chemical assumptions were changed; therefore,
the agreement is evidence in favour of the kinetic features but not of the
structural and chemical ones.
The theory leads naturally to an explanation of the discontinuity
22 A. F. HUXLEY
between shortening and lengthening in the force-velocity curve (point F,
p. 6; Text-fig. 1).
Since this theory was published, two kinds of experimental results have
been obtained which are not explained by it. One of these was A. V. Hill's
finding (1964) that 'shortening heat' was not simply proportional to the
amount of shortening, as had appeared from his results published in 1938,
but was relatively smaller when the speed of shortening was high (Text-
fig. 2). The new results implied (Woledge, 1968) that, as speed of shortening
is raised, the total rate of energy liberation actually passes through a
maximum, and falls at the highest shortening speeds. Chaplain & From-
melt (1971) pointed out, correctly, that this result could not be accom-
modated in the kinetic scheme of my 1957 theory. There are several ways
in which this result might be explained; one which involves only a small
change to the 1957 theory is to assume that attachment is not a single-
stage but a two-stage process (A. F. Huxley, 1973), the cross-bridge being
easily detached, without net chemical change, until the second step has
occurred.
The other group of experimental findings that are not accounted for
by the 1957 theory are the 'transient' responses that can be recorded
when either the load on a muscle fibre, or its length, is suddenly changed.
These are the subject of the following section.
Mechanical transient responses and their interpretation
The idea of investigating the contraction process by imposing a sudden
change of mechanical conditions during a contraction is not new. Experi-
ments of this kind were done by Gasser & Hill (1924) and by Levin &
Wyman (1927), and led to the representation of active muscle as two
components in series, a 'contractile component' and a 'series elastic
component'. Of these, the former was defined as having a definite force-
velocity curve, i.e. at any instant its speed of shortening was determined
entirely by the load on the muscle at that instant. Similarly, the 'series
elastic component' was defined as having a length that was entirely
determined by the load at that instant. The behaviour of a system consist-
ing of these two elements in series is indeed a first approximation to the
behaviour of active muscle, but recent experiments with the much im-
proved time resolution that has become available have shown that the
responses of muscle to sudden changes of load or length are in fact much
more complicated (and correspondingly more interesting) than those of
the two-component model.
' Velocity transients' and 'tension transients'. The first experiments to
show this more complicated behaviour were those of Podolsky (1960;
Civan & Podolsky, 1966). A bundle of fibres was stimulated and held, at
first, at constant length. It was then released suddenly and allowed to
shorten under a definite load, the time course of the change of length
being recorded. There was an initial sudden shortening (as would be
expected from a 'series-elastic component') but after this, the speed of
shortening underwent a complex sequence of changes (the 'velocity
transient') instead of being constant as it should be on the two-component
theory. At first, the speed of shortening was several times higher than the
steady-state value appropriate for the load; it then declined to a low value,
Velocity 3X 4 0n
transient
2
- 2kg/cm2
5 msec
.i
I-
II -.. I Iqw
I110nr
i ! i t....l....i....
Tension
transient ~ 3
{l
X kg/cm2
10 msec
Text-fig. 7. Mechanical transient responses in isolated frog muscle fibres,
during tetanic stimulation. Above: 'velocity transient', i.e. time course of
length change (upper t-ace) when load is suddenly altered (middle t ace).
Bottom trace is tension base line. Below: 'tension transient', i.e. time course
of tension change (middle trace) when length is suddenly altered (upper
trace). Bottom trace is tension base line. The numbers indicate corresponding
phases in the two types of transient response (see text and Table 1).
(From unpublished experiments by A. F. Huxley and R. M. Simmons.)
or might fall to zero or even reverse its direction; and finally it built up
again to its steady-state value, with sometimes a damped oscillation which
can be very conspicuous when the tension is changed only slightly from
its isometric value (Armstrong, A. F. Huxley & Julian, 1966). A more
recent record showing these features, obtained in our laboratory on an
isolated fibre, is shown in Text-fig. 7.
Still better time resolution can be attained in the converse type of
24 A. F. HUXLEY
Text-fig. 8. For legend see facing page.

experiment, in which a sudden small change of length is imposed during an
isometric contraction, and the ensuing tension changes are recorded
(Text-figs. 7 and 8). Again there is a tension change simultaneous with the
length change, as expected from a series-elastic component, and the
subsequent tension recovery - the 'tension transient' - is much more
complex than the nearly exponential time course expected on the two-
component theory. The phases of the recovery are set out in Table 1,
which also shows the way in which they correspond to the phases of the
velocity transient in the other type of experiment.
TABLE 1. Phases of the transient response to sudden reduction of length

('tension transient') or of load '(velocity transient')
Time of Events in Events in
Phase occurrence 'tension transient' 'velocity transient'
1 During applied step Simultaneous drop of Simultaneous shorten-
change tension ing
2 Next 1-2 ms Rapid early tension Rapid early shortening
recovery
3 Next 5-20 ms Extreme reduction or Extreme reduction or
even reversal of rate even reversal of
of tension recovery shortening speed
4 Remainder of the Gradual recovery of Shortening at steady
response tension, with asymp- speed sometimes with
totic approach to superposed damped
isometric tension oscillation
The stated times are appropriate for frog muscle at 50 C approx.
Phase 1 can be attributed to a more or less instantaneous elasticity in

the fibre, though the evidence presented so far does not show where it
resides or whether it is truly 'in series' with a separate contractile
component.
Phases 3 and 4 can be accounted for by detachment and re-attachment
of cross-bridges with kinetics not unlike those postulated in the 1957
theory. Phase 3 would be a period in which both processes are actively at
Text-fig. 8. Family of transients. The records are obtained in the same way
as the bottom two traces in Text-fig. 7, but the time base is 10 times faster
and the step change of length (bottom panel) is complete in 0-2 ms while
the step in Text-fig. 7 took approx. 1 ins.
The distance specified in each of the upper panels is the amount of the
imposed length change in each half-sa-comere. (This Figure, and Text-
figs. 9 and 10, are from recent unpublished experiments by L. E. Ford,
A. F. Huxley and R. M. Simmons.)
26 A. F. HUXLEY
work. Detachment comes to an end first, since it has the higher rate con-
stant (points (c) and (d), p. 20), leaving attachment as the predominant
process in Phase 4. In order for detachment to cause a tendency for tension
to fall (Phase 3), it is necessary to suppose that accelerated detachment
begins when the cross-bridge is still in a position where it exerts positive
tension (A. F. Huxley & Simmons, 1973, pp. 673-4); this is a point of
difference from the 1957 theory. Julian, Sollins & Sollins (1973) have
worked out the time course of tension in Phase 3 and Phase 4 on a theory
of this kind, and obtained curves which resemble those given by real
muscle fibres very closely. I think that this kind of explanation of Phase 3
may well prove correct, though it is not excluded that there may be a
more direct 'de-activation by release' such as is widely postulated to
explain the oscillatory behaviour of the asynchronous flight muscles of
certain insects (Pringle. 1949, 1967).
Phase 2, the early tension recovery in the tension transient, is the aspect
of these phenomena to which our laboratory has so far been paying most
attention. It will be discussed in the next section.
The early tension recovery. Two main types of explanation for this phase
have been put forward. Podolsky and his colleagues (Podolsky, Nolan &
Zaveler, 1969; Podolsky & Nolan, 1973) propose that during an isometric
contraction, many cross-bridges are not attached because thin-filament
sites are not available at the required positions. The sliding movement of
the filaments during the shortening step brings some of these cross-bridges
within range of thin-filament sites; these cross-bridges attach rapidly and
exert tension as soon as they are attached. There is evidence (Huxley &
Simmons, 1971a; Text-fig. 10) that much or all of the instantaneous
compliance (phase 1 of the transients) resides in the cross-bridges, so that
the increase in number of attached cross-bridges postulated by Podolsky
should be accompanied by a decrease in this compliance. Tests made by
applying a second step when the early recovery phase is nearly complete
have shown that the stiffness is no greater than in the isometric condition
(Ford, A. F. Huxley & Simmons, 1974), so we are inclined to think that
little, if any, of the early tension recovery can be attributed to attachment
of cross-bridges that were free up to the moment of the original step change
of length.
The instantaneous tension drop followed by the early tension recovery
is roughly similar to the response of a 'Voigt element', i.e. a spring in
series with a parallel combination of spring and dashpot. If both of the
springs obey Hooke's law, straight lines will be obtained when T1 (the
extreme tension reached simultaneously with the length step) and T2
(the tension approached during the early recovery) are plotted against y,
the amount of the length change. Text-fig. 9 shows that the T1 curve
from a real muscle fibre is in fact nearly straight, becoming a little less
steep as tension gets smaller - a type of behaviour commonly found in the
passive elasticity of biological materials. The T2 curve, however, deviates
grossly from a straight line: for moderate-sized shortening steps it is
almost horizontal, and then curves downwards, approaching a slope
Springs obeying Hooke's Law
14
12
Muscle fibre
08 E
E
0
06 °
04 0
-10 -8 -6 -4 -2 +2
Filament displacement in each half sarcomere (nm)
Text-fig. 9. Above: tension transient response in an ideal Voigt element,
i.e. spring in series with parallel combination of spring and dashpot.
T., extreme tension reached; T2, tension approached asymptotically. Both
T1 and T2 give straight lines when plotted against the size of the imposed
step change of length. Below: T1 and T2 curves constructed from a family
of records such as is shown in Text-fig. 8.
28 A. P. HUXLEY
somewhat less than that of the T1 curve. This immediately suggests that
the structures responsible for the tension recovery are not just passive
visco-elastic elements but are the tension generators themselves, i.e. the
cross-bridges. The fact that the main part of the T2 curve lies some 6 nm
to the left of the T1 curve suggests that some 'active' element in the cross-
bridge is capable of taking up approximately 6 nm of shortening while
maintaining a tension not much less than what it exerts in an isometric
contraction.
As mentioned in the last paragraph, the characteristics of the instant-
aneous elasticity suggest that it is a purely passive property of some part
of the muscle fibre. At first we thought (Huxley & Simmons, 1970) that
1-4
E
0
0
-12 -10 -8 -6 -4 -2 0 +2
Filament displacement in each half-sarcomere (nm)
Text-fig. 10. T, and T2 curves obtained from tension transients recorded
from the same muscle fibre at two different lengths. - , copied from the
lower part of Text-fig. 9; sarcomere length 2-2 /tm, i.e. all cross-bridges
are overlapped by thin filaments. +, T1, and x, T2, from the same fibre
stretched to sarcomere length 3-1 ,tm, i.e. overlap reduced to approx. 39 %.
Interrupted curves: scaled down from the continuous curves by the factor
0 39.
If the filament structure were completely rigid and each cross-bridge
overlapped by thin filament produced the same contribution to the
tension, whatever the fibre length, then the points should fall on the
scaled-down curve; it is seen that they do so to a fair degree of approxi-
mation. This interpretation implies that the elastic component, as well as
the active element, is located within the cross-bridges themselves. If, for
example, the elastic element were separate from the cross-bridges and had
properties independent of the degree of stretch of the fibre, the T, curve
would be displaced to the right at the increased length, instead of becoming
scaled down.
it resided in the filaments and perhaps the Z line, constituting a true 'series
elastic component' whose properties were independent of the state of the
force generators themselves. There was, however, nothing to exclude the
possibility that it was due to some part of the cross-bridges. In order to
decide between these possibilities, we recorded tension transients during
tetani with the fibre stretched to different lengths, i.e. with reduced
amounts of overlap of thick and thin filaments. The result was simple
(Huxley & Simmons, 1971 a; Text-fig. 10): both the T1 and T2 curves
scaled down in direct proportion to the amount of overlap. The straight-
forward interpretation is that the instantaneous elasticity, as well as the
early recovery, is attributable to the cross-bridges, the filament arrays
being almost completely rigid. The filaments must of course possess some
compliance, and it is difficult to put a limit to its possible amount, but we
think it unlikely to be large enough to lead to serious error if, as a first
approximation, it is disregarded. We therefore assume, provisionally,
that the whole of the instantaneous compliance resides in some component
of the cross-bridges.
Two components within each cross-bridge. Thus, each cross-bridge seems
to contain (1) an instantaneous elastic element, and (2), in series with it,
an element which can maintain tension while taking up limited but sub-
stantial amounts of length change. The total range over which element
(2) actively generates movement is probably 10-12 nm; it is likely to be
greater than the 6 nm mentioned above because, after attaching, it
presumably has to generate a movement of the order of 5 nm so as to
stretch the elastic element, even in an isometric contraction. This estimate
of the range of action agrees as well as can be expected with the values
calculated by H. E. Huxley (1960, p. 452) and by Davies (1963) from esti-
mates of the tension per cross-bridge and the work that can be done per
mole of ATP utilized. They assume (as do most authors) that one molecule
of ATP is hydrolysed per cross-bridge cycle. Tonomura (1972, p. 390),
however, proposes a cycle that utilizes two molecules of ATP, which would
require the range of action to be twice as great.
Can a cross-bridge exert negative tension? Another interesting feature of
the T1 curve is that it approaches the base line at a definite angle and not
tangentially or asymptotically. The measured T. values are all higher
than they would be if a truly instantaneous length step were applied, since
the early recovery begins before the step is complete, and this effect is
relatively greater in the large steps because the early recovery is more
rapid (see below). The true T1 curve is therefore straighter (and steeper)
than what we have been able to record, and it would approach the
abscissa in an even more angular manner than is seen in Text-fig. 9.
Blange, Karemaker & Kramer (1972) claimed that the curve approached
30 A. F. HUXLEY
the base line tangentially, and interpreted this by supposing that cross-
bridges could not support negative tension and that more and more of
them became slack as the size of shortening step was increased, reducing
the stiffness of the fibre and therefore the slope of the T1 curve. Our
results do not confirm Blange et al. (1972), and the fact that we find a
sharp approach to the base line is evidence that the cross-bridges are able
to exert negative tension.
Evidence for stepwise action. When the time course of the early tension
recovery is examined (Text-fig. 8), another interesting non-linear feature
a
I
I
11
Thick filament Thick filament -
LMM S LMM I- 2
s-I1 2 s-I 2
Thin filament-.- Thin filament-

11
Text-fig. 11. a, diagram of active cross-bridges adapted from H. E. Huxley

(1969). He proposed that the force originates in a tendency for the myosin
head (S.1) to rotate relative to the thin filament, and is transmitted to the
thick filament by the S-2 portion of the myosin molecule acting as an
inextensible link. Flexible points at each end of S-2 permit S-1 to rotate,
and allow for variations in the separation between filaments.
b, development from a proposed by A. F. Huxley & Simmons (1971 b)
to incorporate the elastic and stepwise-shortening elements for which they
gave evidence derived from tension transients. The strength of binding of the
attached sites are higher in position 2 than position 1, and in position 3
than position 2. During isometric contraction the myosin head oscillates
rapidly between its three stable positions. The myosin head can be detached
from position 3 with the utilization of a molecule of ATP; this is the
predominant process during shortening. During stretch, the myosin head
can dissociate from position 1 without utilization of ATP.
makes itself evident. The half-time of the early tension recovery is shortest
in a large release, becoming progressively longer as the size of the release is
decreased, and longer still in stretches, the variation being continuous over
the whole range that can be investigated. The following explanation was
proposed by A. F. Huxley & Simmons (1971 b). Shortening of element (2)
of the cross-bridge takes place by rapid switching from one to the next
of a series of perhaps 2, 3 or 4 states, which have progressively lower
potential energy. These switching movements are reversible, and in the
isometric state an equilibrium is set up, each cross-bridge dividing its
time between the various states under the influence of (a) the potential
energy differences, tending to cause forward movement and (b) the tension
in the elastic element (1) tending to cause backward movement. To make a
forward switching movement, the cross-bridge requires activation energy
not only to escape from the state it is already in, but also to do the work
of stretching the elastic element far enough for it to get into the new state.
The work term therefore appears as a component of the activation energy
for a forward movement; the higher the tension, the greater the activation
energy and therefore the slower the rate of transfer to the next position.
The greater a shortening step, the less the tension in each elastic element,
and therefore the less the activation energy for the forward stepping
movement of element (2). This motion therefore occurs more rapidly,
and shows itself as an early recovery phase with shorter half-time.
Relation to structural and chemical information. The most widely accepted
view of the structure of a cross-bridge is that proposed by H. E. Huxley
(1969, 1971) on the basis of observations (largely his own) by electron
microscopy and low-angle X-ray diffraction. Text-fig. 11 a is an adaptation
of his diagram. An important and suggestive feature of his proposal is
that the force originates in a tendency for the myosin head to rotate about
its point of attachment to the thin filament, and is transmitted to the thick
filament by 'sub-fragment 2' of the myosin molecule which acts as a
link. In H. E. Huxley's account, this link is assumed inextensible,
and the connexions at its ends to the other parts of the myosin molecule
are assumed freely flexible.
Can the instantaneous elastic element (1) and the stepwise shortening
element (2), whose existence is suggested by the tension transients, be
identified with particular parts of this structure? Simmons and I (Huxley
& Simmons, 1971 b) tentatively proposed the arrangement shown in
Text-fig. 11 b, i.e. the elastic element is in S-2 and the stepping move-
ment occurs by rotation of the whole myosin head relative to the thin
filament. I do not know of any evidence against this suggestion, and I
still use it in my own thinking about the contractile mechanism. But it is
important to remember that there is no specific evidence in favour of it,
2 P H Y 243
32 A. F. HUXLEY
and that many other possibilities are open. Even within H. E. Huxley's
scheme, it might be, for example, that the actual attachment between
actin and myosin is rigid and that the stepwise rotations occur at joints
within the myosin head (Text-fig. 12 a). Again, the instantaneous elasticity
might be within the thin filament (Text-fig. 12b) in the form of an angular
compliance between the backbone of the filament and the part of the
structure to which the myosin head attaches. Some other possibilities are
enumerated by A. F. Huxley & Simmons (1973), and any ingenious person
could make additions to the list. When we consider permutations of the
possible structural bases for elements (1) and (2), the number of options
becomes enormous. Studies of the kinetics of contraction, of the kind that
I have been discussing in this lecture, cannot answer questions of this sort:
more information is needed about the internal structure of the actin and
a b
f0011 1 11
wihn h yoi_ ha.Th_ latcelmn 0a
totetin fiamn irgd, an th,,pie oeettae lc
Texant-fg.12ra alternative to Fig. 11 b asha strucurabsis

moveen is produxled
in the same way as in Fig. II b, but the elastic element is provided by
rotation, relative to the rest of the thin filament, of the piece to which
the myosin head attaches.
myosin molecules, and about the positions of the parts of the myosin
molecule during contraction. The latter may come from X-ray diffraction
or from electron microscopy, or from optical or spin-resonance measure-
ments of the orientation of components of the myosin molecule or of small
molecules attached to it (Seidel & Gergely, 1973; Botts et al. 1973; Steiger
et al. 1973; Carlson et at. 1973).
Relation to chemical events. If the idea of a stepwise movement of (or
within) the myosin molecule is correct, it becomes necessary to suppose
that the stepping is somehow coupled to the hydrolysis of ATP. Much is
now known about intermediate stages in the enzymic hydrolysis of ATP
by the actomyosin ATPase, both from steady-state studies (e.g. Moos,
1973) and from kinetic experiments (reviewed by Tonomura (1972),
E. W. Taylor (1972) and Bagshaw et al. (1973)). As has already been
mentioned, one of the conspicuous actions of ATP is to cause actomyosin
to dissociate; on a scheme such as the one shown in Text-fig. 11 b this action
would be sufficient to drive the system, if it is assumed that this disso-
ciation can only be brought about when the myosin head has moved to
its final position (most clockwise position in Text-fig. 1 b). If, however,
the stepping movement involves some internal re-arrangement within the
myosin molecule (as in Text-fig. 12 a), it becomes necessary to postulate
either that this rearrangement is coupled to some stage of the hydrolysis
of the ATP molecule, or else that the rearrangement occurs spontaneously
and is reversed before the next cycle by coupling to ATP hydrolysis. The
proposal of Tonomura et al. (1961) requires the hydrolysis of two ATP
molecules per cycle, one to drive the conformational change and the other
to detach the myosin head from the thin filament.
There is at present no evidence to show which (if any) of these ways in
which ATP hydrolysis might be coupled to movement is correct. I think
that most biochemists at the present day would favour the idea that some
' conformational change' occurs in the myosin molecule soon after it binds
an ATP molecule, bringing it into a state which can do mechanical work
when it becomes attached to a thin filament. The meaning of the word
'conformational ', however, has become so broad that this statement would
be true whatever the nature of the effect on a myosin molecule of binding
an ATP - whether it was a gross shape change whose reversal could do
mechanical work, or a shift of electrons that leads to a change of affinity
for binding sites on the thin filament. I am reminded of the remark attribu-
ted to Dean Inge (Mencken, 1936), that the word 'bloody' had become
'simply a sort of notice that a noun may be expected to follow': 'con-
formational' has become simply a notice that the word 'change' may be
expected to follow.
In this sense, the theory that the key event is a 'conformnational change'
2-2
34 A. F. HUXLEY
induced in the myosin molecule by some stage of the process of ATP
hydrolysis, will almost inevitably be confirmed. Meanwhile, it is an un-
helpful hypothesis because it does not specify what sort of change is to
be looked for.
CONCLUSION
In the summer of 1972, a highly successful symposium on 'The Mech-
anism of Muscle Contraction' was held at Cold Spring Harbor. Everyone
who was there felt at the end that he knew a lot more about muscle
contraction than he had known before the meeting, and the book produced
from the contributions is a most valuable record of the present position
in most aspects of the field. But I was horrified to hear several of the
participants saying that 'the problem of muscle contraction is solved in
principle'. Even if the points set out in the Summary (para. 4) all turn
out to be true, they only take one perhaps half way to a real understanding
of how muscle contracts: for example, we do not know any of the following.
1. Which structure is the elastic element in the cross-bridge.
2. What is the nature of this elasticity.
3. What structure undergoes the stepwise change.
4. Whether the attachment of the myosin head is to a single actin
monomer, or to two (or more) monomers within the thin filament.
5. What kind of bonds hold the myosin head to the thin filament.
6. How binding of ATP causes myosin to dissociate from actin.
7. What is the significance of the fact that each myosin molecule has
two heads.
And, quite apart from the fact that all these things are unknown, the
whole history of theories of muscular contraction during the last half
century shows that even when a set of ideas seems to be well established,
there is a large chance that it will be overthrown by some unexpected
discovery.
SUMMARY
1. A resume of the events in excitation and in excitation-contraction
coupling is given.
2. The theory that length changes in striated muscle take place pre-
dominantly by relative sliding movements of two sets of submicroscopic
filaments was proposed in 1953-54 and was soon firmly established, dis-
placing the idea of continuous filaments of actomyosin that shortened by
folding.
3. Many proposals have been made for the mechanism by which the
sliding movement is brought about during contraction.
4. A coherent, though still incomplete, theory is presented. Evidence
(in many cases dating from before 1945) is given for each of the following
features:
a, shortening and the development of tension are produced by inde-
pendent force-generators distributed in each zone of overlap,
b, these force-generators are identified with the cross-bridges seen in
the electron microscope,
c, within a single contraction, each force-generator may act repeatedly
in cycles of attachment, pulling, and detachment,
d, detachment is brought about during a contraction by interaction
with ATP,
e, detachment by ATP is slow until shortening has allowed the cross-
bridge to perform the working part of its stroke,
f, the rate constant for attachment is moderate,
g, attachment is reversible, without utilization of ATP, if the cross-
bridge is prevented from performing its working stroke,
h, each cross-bridge contains a non-linear element which takes up some
6 nm of shortening in I.1 Ims,
i, within each cross-bridge there is an elastic element in series with this
non-linear element,
j, the filaments themselves are so stiff that their compliance is near to
being negligible, and
k, the non-linear element in each cross-bridge makes its movement in a
small number of steps.
5. None of these points should be regarded at the present day as being
established beyond doubt, and many important matters are quite un-
known, e.g. the structural identification of the elements postulated from
mechanical observations, and the nature of the bonds between actin and
myosin.
Of the observations and ideas discussed in this review, those which originated
in my laboratory owe much to a long series of collaborators, whose names appear
in the References.
I also wish to thank Dr A. M. Gordon for letting me reproduce the photo-
graphs which appear as PI. 1, and my present co-workers Dr R. M. Simmons and
Dr L. E. Ford for letting me include some unpublished records from our latest series
of experiments.
I gratefully acknowledge permission from the Central Office of Information,
London. to reproduce the frontispiece.
36 A. F. HUXLEY
REFERENCES
ABBOTT, B. C. & AuIBERT, X. M. (1951). Changes of energy in a muscle during very
slow stretches. Proc. R. Soc. B 139, 104-117.
ABBOTT, B. C., AUBERT, X. M. & HILL, A. V. (1951). The absorption of work by a
muscle stretched during a single twitch or a short tetanus. Proc. R. Soc. B 139,
86-104.
ADRIAN, E. D. (1922). The relation between the stimulus and the electric response
in a single muscle fibre. Archs ngerl. Physiol. 7, 330-332.
ADRIAN, R. H. & PEACHEY, L. D. (1973). Reconstruction of the action potential of
frog sartorius muscle. J. Physiol. 235, 103-131.
ARMSTRONG, C. M., HUXLEY, A. F. & JULIAN, F. J. (1966). Oscillatory responses in
frog skeletal muscle fibres. J. Physiol. 186, 26-27P.
ARRONET, N. I. (1973). Motile Muscle and Cell Models (translated from Russian by
B. Haigh). New York and London: Consultants Bureau.
ASAKURA, S., TANIGUCHI, M. & OOSAWA, F. (1963). Mechano-chemical behaviour
of F-actin. J. molec. Biol. 7, 55-69.
ASHLEY, C. C. & RIDOWAY, E. B. (1970). On the relationships between membrane
potential, calcium transient and tension in single barnacle muscle fibres. J. P. hysiol.
209, 105-130.
ASTBURY, W. T. (1947). On the structure of biological fibres and the problem of
muscle. Proc. R. Soc. B 134, 303-328.
ATWOOD, H. L., HOYLE, G. & SMYTH, T. Jr. (1965). Mechanical and electrical
responses of single innervated crab-muscle fibres. J. Physiol. 180, 449-482.
AUBER, J. & COUTEAUX, R. (1963). Ultrastructure de la strie Z dans des muscles
de dipteres. J. Microscopie 2, 309-324.
AUBERT, X. (1944a). La chaleur degagee par un muscle soumis A un travail en cycle.
C. r. Sganc. Soc. Biol. 138, 1011-1013.
AUBERT, X. (1944b). L'influence du delai de relachement sur la chaleur d6gag6e
par un muscle soumis a un travail en cycle. C. r. Sganc. Soc. Biol. 138, 1048-1050.
AUBERT, X. (1948). Reversibilite partielle de la contraction musculaire au cours de
l'absorption du travail en cycle. Archs int. Phy8iol. 55, 348-361.
AUBERT, X. & LEBACQ, J. (1971). The heat of shortening during the plateau of
tetanic contraction and at the end of relaxation. J. Physiol. 216, 181-200.
BAGSHAW, C. R., ECCLESTON, J. F., TRENTHAM, D. R., YATES, D. W. & GOODY, R. S.
(1973). Transient kinetic studies of the Mg++-dependent ATPase of myosin and
its proteolytic subfragments. Cold Spring Harb. Symp. quant. Biol. 37, 127-135.
BAILEY, K. (1948). Tropomyosin: a new asymmetric protein component of the
muscle fibril. Biochem. J. 43, 271-279.
BARANY, E. H., EDMAN, K. A. P. & PALIS, A. (1952). The influence of electrolytes
on the rate of viscosity drop in ATP-actomyosin mixtures. Acta physiol. scand.
24, 361-367.
BLANCo, T., KAREMAKER, J. M. & KRAMER, A. E. J. L. (1972). Elasticity as an
expression of cross-bridge activity in rat muscle. Pflugers Arch. 336, 277-288.
BOTTS, J., COOKE, R., DOS REMEDIOS, C., DUKE, J., MENDELSON, R., MORALES,
M. F., TOKIWA, T. & VINIEGRA, G. (1973). Does a myosin cross-bridge progress
a-m-over-arm on the actin filament? Cold Spring Harb. Symp. quant. Biol. 37,
195-200.
BROWN, L. M., GONZALEZ-SERRATOS, H. & HUXLEY, A. F. (1970). Electron micro-
scopy of frog muscle fibres in extreme passive shortening. J. Physiol. 208, 86-88P.
BUCHTHAL, F. & KAISER, E. (1951). The rheology of the cross striated muscle fibre
(pp. 233-291). Biol. meadr 21, no. 7.
CAIN, D. F., INFANTE, A. A. & DAVIES, R. E. (1962). Chemistry of muscle contrac-
tion. Adenosine triphosphate and phosphorylcreatine as energy supplies for single
contractions of working muscle. Nature, Lond. 196, 214-217.
CARLSEN, F., KNAPPEIS, G. G. & BUCHTHAL, F. (1961). Ultrastructure of the resting
and contracted striated muscle fiber at different degrees of stretch. J. biophy8.
biochem. Cytol. 11, 95-117.
CARLSON, F. D., BONNER, R. & FRASER, A. (1973). Intensity fluctuation auto.
correlation studies of resting and contracting frog sartorius muscle. Cold Spring
Harb. Symp. quant. Biol. 37, 389-396.
CASELLA, C. (1950). Tensile force in total striated muscle, isolated fibre and sarco-
lemma. Acta physiol. 8cand. 21, 380-401.
CHAPLAIN, R. A. & FROMMELT, B. (1971). A mechanochemical model for muscular
contraction. I. The rate of energy liberation at steady state velocities of shortening
and lengthening. J. Mechanochem. Cell Motility 1, 41-56.
CIVAN, M. M. & PODOLSKY, R. J. (1966). Contraction kinetics of striated muscle
fibres following quick changes in load. J. Physiol. 184, 511-534.
COSTANTIN, L. L. (1970). The role of sodium current in the radial spread of con-
traction in frog muscle fibers. J. gen. Physiol. 55, 703-715.
COSTANTIN, L. L. & TAYLOR, S. R. (1971). Active and passive shortening in voltage-
clamped frog muscle fibres. J. Physiol. 218, 13-15P.
CURTIN, N. A. & DAVIES, R. E. (1973). Chemical and mechanical changes during
stretching of activated frog skeletal muscle. Cold Spring Harb. Symp. quant. Biol.
37, 619-626.
DAINTY, M., KLEINZELLER, A., LAWRENCE, A. S. C., MIALL, M., NEEDHAM, J.,
NEEDHAM, D. M. & SHEN, S.-C. (1944). Studies on the anomalous viscosity and
flow-birefringence of protein solutions. III. Changes in these properties of myosin
solutions in relation to adenosinetriphosphate and muscular contraction. J. gen.
Physiol. 27, 355-399.
DAVIES, R. E. (1963). A molecular theory of muscle contraction: calcium-dependent
contractions with hydrogen bond formation plus ATP-dependent extensions of
part of the myosin-actin cross-bridges. Nature, Lond. 199, 1068-1074.
DESHCHEREVSKII, V. J. (1968). Two models of muscular contraction. Biophysics 13
(1969), 1093-1101.
DICKINSON, V. A. & WOLEDGE, R. C. (1973). The thermal effects of shortening in
tetanic contractions of frog muscle. J. Physiol. 233, 659-671.
EBASHI, S. (1963). Third component participating in the superprecipitation of
'natural actomyosin'. Nature, Lond. 200, 1010.
EBASHI, S. & ENDO, M. (1968). Calcium ion and muscle contraction. Prog. Biophys.
molec. Biol. 18, 123-183.
EBASHI, S., ENDO, M. & OHTSUKI, I. (1969). Control of muscle contraction. Q. Rev.
Biophys. 2, 351-384.
EBASHI, S. & KODAMA, A. (1965). A new protein factor promoting aggregation of
tropomyosin. J. Biochem. 58, 107-108.
ELLIOTT, G. F., RoME, E. M. & SPENCER, M. (1970). A type of contraction hypothesis
applicable to all muscles. Nature, Lond. 226, 417-420.
ENDO, M. (1964). Entry of a dye into the sarcotubular system of muscle. Nat'gre,
Lond. 202, 1115-1116.
ENDO, M. (1966). Entry of fluorescent dyes into the sarcotubular system of the frog
muscle. J. Physiol. 185, 224-238.
ENGELHARDT, V. A. & LyuBIMOVA, M. N. (1939). Myosine and adenosinetriphos-
phatase. Nature, Lond. 144, 668-669.
38 A. F. HUXLEY
ENGELHARDT, V. A., LYUBIMOVA, M. N. & MEITINA, R. A. (1941). Chemistry and
mechanics of the muscle studied on myosin threads. Dokl. Akad. Nauk SSSR 30,
644.
FENN, W. 0. (1923). A quantitative comparison between the energy liberated and
the work performed by the isolated sartorius muscle of the frog. J. Phy8iol. 58,
175-203.
FENN, W. 0. (1924). The relation between the work performed and the energy
liberated in muscular contraction. J. Physiol. 58, 373-395.
FENN, W. 0. & MARSH, B. S. (1935). Muscular force at different speeds of shortening.
J. Phyaiol. 85, 277-297.
FIELDS, R. W. & FABER, J. J. (1970). Biophysical analysis of the mechanical
properties of the sarcolemma. Can. J. Phy8iol. Pharmacol. 48, 394-404.
FORD, L. E., HUXLEY, A. F. & SIMMONS, R. M. (1974). Mechanism of early tension
recovery after a quick release in tetanized muscle fibres. J. Phy8iol. 240, 42-43P.
FRANZINI-ARMSTRONG, C. & PORTER, K. R. (1964). Sarcolemmal invaginations
constituting the T system in fish muscle fibers. J. Cell Biol. 22, 675-696.
GASsER, H. S. & HILL, A. V. (1924). The dynamics of muscular contraction. Proc.
R. Soc. B 96, 398-437.
GELFAN, S. (1931). Studies of single muscle fibres. III. Further evidence of graded
responses in single fibres. Am. J. Phy8iol. 96, 16-20.
GELFAN, S. (1933). The submaximal responses of the single muscle fibre. J. Phy8iol.
80, 285-295.
GILBERT, C., KRETZSCHMAR, K. M., WILKIE, D. R. & WOLEDGE, R. C. (1971).
Chemical change and energy output during muscular contraction. J. Physiol.
218, 163-193.
GONZkLEZ-SERRATOS, H. (1971). Inward spread of activation in vertebrate muscle
fibres. J. Physiol. 212, 777-799.
GORDON, A. M., HUXLEY, A. F. & JULIAN, F. J. (1966a). Tension development in
highly stretched vertebrate muscle fibres. J. Physiol. 184, 143-169.
GORDON, A. M., HUXivY, A. F. & JULIAN, F. J. (1966b). The variation in isometric
tension with sarcomere length in vertebrate muscle fibres. J. Phy8iol. 184, 170-192.
HALL, C. E., JAKus, M. A. & SCHMITT, F. 0. (1946). An investigation of cross
striations and myosin filaments in muscle. Biol. Bull. mar. biol. Lab. Wood8 Hole
90, 32-50.
HANSON, J. (1968). Recent X-ray diffraction studies of muscle. Q. Rev. Biophy&. 1,
177-216.
HANSON, J. & HUXLEY, H. E. (1953). Structural basis of the cross-striations in
muscle. Nature, Lond. 172, 530-532.
HANSON, J. & HUXLEY, H. E. (1955). The structural basis of contraction in striated
muscle. Symp. Soc. exp. Biol. 9, 228--264.
HARMAN, J. W. (1954). Contractions of skeletal muscle myofibrils by phase micro-
scopy. Fedn Proc. 13, 430.
HASSELBACH, W. (1953). Elektronenmikroskopische Untersuchungen an Muskel-
fibrillen bei totaler und partieller Extraktion des L-Myosins. Z. Naturf. 8b,
449-454.
HILL, A. V. (193S). The heat of shortening and the dynamic constants of muscle.
Proc. R. Soc. B 126, 136-195.
HILL, A. V. (1949 a). The heat of activation and the heat of shortening in a muscle.
twitch. Proc. R. Soc. B 136, 195-211.
HILL, A. V. (1949 b). Work and heat in a muscle twitch. Proc. R. Soc. B 136, 220-228.
HILL, A. V. (1964). The effect of load on the heat of shortening of muscle. Proc. R.
Soc. B 159, 297-318.
HILL, A. V. (1965). Trails and Trials in Physiology. London: Arnold.
HruL, A. V. & HOWARTH, J. V. (1959). The reversal of chemical reactions in con-
tracting muscle during an applied stretch. Proc. R. Soc. B 151, 169-193.
HILL, D. K. (1964). The space accessible to albumin within the striated muscle
fibre of the toad. J. Physiol. 175, 275-294.
HODGKIN, A. L. (1951). The ionic basis of electrical activity in nerve and muscle.
Biol. Rev. 26, 339-409.
HOYLE, G. (1968). In Symposium on Mwucle, ed. ERNST, E. & STRAUB, F. B.,
pp. 34-48. Budapest: Akad6mia-i Kiad6.
HUXLEY, A. F. (1952). Applications of an interference microscope. J. Physiol. 117,
52-53P.
HUXLEY, A. F. (1954). A high-power interference microscope. J. Physiol. 125,
11-13P.
HUXLEY, A. F. (1957). Muscle structure and theories of contraction. Prog. Biophys.
biophys. Chem. 7, 255-318.
HUXLEY, A. F. (1973). A note suggesting that the cross-bridge attachment during
muscle contraction may take place in two stages. Proc. R. Soc. B 183, 83-86.
HUXLEY, A. F. & GORDON, A. M. (1962). Striation patterns in active and passive
shortening of muscle. Nature, Lond. 193, 280-281.
HUXLEY, A. F. & JuLIAN, F. J. (1964). Speed of unloaded shortening in frog striated-
muscle fibres. J. Physiol. 177, 60-61 P.
HUXLEY, A. F. & NIEDERGERKE, R. (1954). Interference microscopy of living
muscle fibres. Nature, Lond. 173, 971-973.
HUXLEY, A. F. & NIEDERGERKE, R. (1958). Measurement of the striations of isolated
muscle fibres with the interference microscope. J. Physiol. 144, 403-425.
HUXLEY, A. F. & PEACHEY, L. D. (1961). The maximum length for contraction in
vertebrate striated muscle. J. Physiol. 156, 150-165.
HUXLEY, A. F. & SImMONs, R. M. (1970). A quick phase in the series-elastic com-
ponent of striated muscle, demonstrated in isolated fibres from the frog. J. Physiol.
208, 52-53P.
HUXLEY, A. F. & SIMMONs, R. M. (1971a). Mechanical properties of the cross-bridges
of frog striated muscle. J. Physiol. 218, 59-60P.
HUXLEY, A. F. & SIMMONs, R. M. (1971 b). Proposed mechanism of force generation
in striated muscle. Nature, Lond. 233, 533-538.
HUXLEY, A. F. & SIMMONs, R. M. (1973). Mechanical transients and the origin of
muscular force. Cold Spring Harb. Symp. quant. Biol. 37, 669-680.
HUXLEY, A. F. & STRAUB, R. W. (1958). Local activation and interfibrillar structures
in striated muscle. J. Physiol. 143, 40-41P.
HUXLEY, A. F. & TAYLOR, R. E. (1955). Function of Krause's membrane. Nature,
Lond. 176, 1068.
HUXLEY, A. F. & TAYLOR, Et. E. (1958). Local activation of striated muscle fibres.
J. Physiol. 144, 426-441.
HUXLEY, H. E. (1953a). X-ray analysis and the problem of muscle. Proc. R. Soc.
B 141, 59-62.
HUXLEY, H. E. (1953b). Electron microscope studies of the organisation of the
filaments in striated muscle. Biochim. biophys. Acta 12, 387-394.
HUXLEY, H. E. (1957). The double array of filaments in cross-striated muscle.
J. biophys. biochem. Cytol. 3, 631-648.
HUXLEY, H. E. (1960). Muscle Cells. In The Cell, vol. iv, ed. BRACHET, J. & MIRSKY,
A. E., pp. 365-481. New York: Academic Press.
HUXLEY, H. E. (1963). Electron microscope studies on the structure of natural
and synthetic protein filaments from striated muscle. J. molec. Biol. 7, 281-308.
40 A. F. HUXLEY
HUXLEY, H. E. (1964a). Evidence for continuity between the central elements of
the triads and extracellular space in frog sartorius muscle. Nature, Lond. 202,
1067-1071.
HUXLEY, H. E. (1964b). Structural arrangements and the contraction mechanism in
striated muscle. Proc. R. Soc. B 160, 442-448.
HUXLEY, H. E. (1969). The mechanism of muscular contraction. Science, N.Y. 164,
1356-1366.
HUXLEY, H. E. (1971). The structural basis of muscular contraction. Proc. R. Soc.
B 178, 131-149.
HUXLEY, H. E. & BROWN, W. (1967). The low-angle X-ray diagram of vertebrate
striated muscle and its behaviour during contraction and rigor. J. molec. Biol. 30,
383-434.
HUXLEY, H. E. & HANSON, J. (1954). Changes in the cross-striations of muscle
during contraction and stretch and their structural interpretation. Nature, Lond.
173, 973-976.
HUXLEY, H. E. & HANSON, J. (1957). Quantitative studies on the structure of
cross-striated myofibrils. I. Investigations by interference microscopy. Biochim.
biophy8. Acta 23, 229-249.
JASPER, H. H. & PEZARD, A. (1934). Relation entre la rapidity d'un muscle
strike et sa structure histologique. C. r. hebd. SNanc. Acad. Sci., Paria 198, 499-501.
JOBSIS, F. F. & O'CONNOR, M. J. (1966). Calcium release and reabsorption in the
sartorius muscle of the toad. Biochem. biophys. Re8. Commun. 25, 246-252.
JORDAN, H. E. (1934). Structural changes during contraction in the striped muscle
of the frog. Am. J. Anat. 55, 117-133.
JULIAN, F. J., SOLLINS, K. R. & SOLLINS, M. R. (1973). A model for muscle
contraction in which cross-bridge attachment and force generation are distinct.
Cold Spring Harb. Symp. quant. Biol. 37, 685-688.
KATZ, B. (1939). The relation between force and speed in muscular contraction.
J. Physiol. 96, 45-64.
KUFFLER, S. W. (1946). The relation of electric potential changes to contracture in
skeletal muscle. J. Neurophysiol. 9, 367-377.
KtHNE, W. (1864). Untersuchungen uiber das Protoplama und die Contractilitdt.
Leipzig: Engelmann.
KUSHMERICK, M. J., LARSON, R. E. & DAVIES, R. E. (1969). The chemical energetic
of muscle contraction. I. Activation heat, heat of shortening and ATP utilization
for activation-relaxation processes. Proc. R. Soc. B 174, 293-313.
LEVIN, A. & WYMAN, J. (1927). The viscous elastic properties of muscle. Proc. R.
Soc. B 101, 218-243.
LYMN, R. W. & TAYLOR, E. W. (1971). Mechanism of adenosine triphosphate
hydrolysis by actomyosin. Biochemistry 10, 4617-4624.
MCCLARE, C. W. F. (1971). Chemical machines, Maxwell's demon and living
organisms. J. theor. Biol. 30, 1-34.
MCCLARE, C. W. F. (1972). A 'molecular energy' muscle model. J. theor. Biol. 35,
569-595.
MONEILL, P. A. & HOYLE, G. (1967). Evidence for superthin filaments. Am. Zool. 7,
483-498.
MATSUBARA, I. & ELLIOTT, G. F. (1972). X-ray diffraction studies on skinned single
fibres of frog skeletal muscle. J. molec. Biol. 72, 657-669.
MENCKEN, H. L. (1936). The American Language, 4th edn. p. 312. New York:
A. A. Knopf.
MEYER, K. H. (1929). 'Ober Feinbau, Festigkeit und Kontraktilitat tierischer
Gewebe. Biochem. Z. 214, 253-281.
MOMMAERTS, W. F. H. M. (1951). The scattering of light in myosin solutions.
I. The angular dissymmetry and the molecular length. J. biol. Chem. 188,
553-557.
MOMMAERTS, W. F. H. M. (1956). The effect of adenosinetriphosphate upon acto-
myosin solutions, studied with a recording dual beam light-scattering photometer.
J. gen. Physiol. 39, 821-830.
Moos, C. (1973). Actin activation of heavy meromyosin and subfragment-1 ATPases;
steady state kinetics studies. Cold Spring Harb. Symp. quant. Biol. 37, 137-143.
MORALES, M. & BOTTS, J. (1952). A model for the elementary process in muscle
action. Archs Biochem. Biophys. 37, 283-300.
NEEDHAM, D. M. (1950). Myosin and adenosinetriphosphate in relation to muscle
contraction. Biochim. biophys. Acta 4, 42-49.
NEEDHAM, D. M. (1971). Machina Carnis. The Biochemistry of Muscular Contraction
in its Historical Development. Cambridge: University Press.
NEEDHAM, J., SHEN, S.-C., NEEDHAM, D. M. & LAWRENCE, A. S. C. (1941). Myosin
birefringence and adenylpyrophosphate. Nature, Lond. 147, 766-768.
OPLATKA, A. (1972). On the mechanochemistry of muscular contraction. J. theor.
Biol. 34, 379-403.
PAGE, S. (1964). The organization of the sarcoplasmic reticulum in frog muscle.
J. Physiol. 175, 10-1IP.
PAGE, S. G. (1968). Fine structure of tortoise skeletal muscle. J. Physiol. 197,
709-715.
PAGE, S. G. (1969). Structure and some contractile properties of fast and slow
muscles of the chicken. J. Physiol. 205, 131-145.
PAGE, S. G. & HUXLEY, H. E. (1963). Filament lengths in striated muscle. J. Cell
Biol. 19, 369-390.
PODOLSiY, R. J. (1959). The chemical thermodynamics and molecular mechanism
of muscular contraction. Ann. N.Y. Acad. Sci. 72 (12), 522-537.
PODOLSxY, R. J. (1960). Kinetics of muscular contraction: the approach to the
steady state. Nature, Lond. 188, 666-668.
PODOLSKY, R. J. (1964). The maximum sarcomere length for contraction of isolated
myofibrils. J. Physiol. 170, 110-123.
PODOLSKY, R. J. & NOLAN, A. C. (1973). Muscle contraction transients, cross-bridge
kinetics, and the Fenn effect. Cold Spring Harb. Symp. quant. Biol. 37, 661-668.
PODOLSKY, R. J., NOLAN, A. C. & ZAVELER, S. A. (1969). Cross-bridge properties
derived from muscle isotonic velocity transients. Proc. natn. Acad. Sci. U.S.A.
64, 504-511.
PoLissAR, M. J. (1952). Physical chemistry of contractile process in muscle. I-IV.
Am. J. Physiol. 168, 766-811.
PORTZEHL, H. (1950). Masse und Masze des L-Myosins. Z. Naturf. 5b, 75-78.
PRINGLE, J. W. S. (1949). The excitation and contraction of the flight muscles of
insects. J. Physiol. 108, 226-232.
PRiNGLE, J. W. S. (1967). The contractile mechanism of insect fibrillar muscle.
Prog. Biophys. molec. Biol. 17, 1-60.
PRYOR, M. G. M. (1950). Mechanical properties of fibres and muscles. Prog. Biophys.
biophys. Chem. 1, 216-268.
RAMSEY, R. W. & STREET, S. F. (1940). The isometric length-tension diagram of
isolated skeletal muscle fibers of the frog. J. cell. comp. Physiol. 15, 11-34.
RAPOPORT, S. I. (1972). Mechanical properties of the sarcolemma and myoplasm in
frog muscle as a function of sarcomere length. J. gen. Physiol. 59, 559-585.
RIcE, R. V. (1961). Conformation of individual macromolecular particles from
myosin solutions. Biochim. biophys. Acta 52, 602-604.
42 A. F. HUXLEY
RIDGWAY, E. B. & ASHLEY, C. C. (1967). Calcium transients in single muscle fibers.
Biochem. biophys. Re8. Commun. 29, 229-234.
ROWE, A. J. (1964). The contractile proteins of skeletal muscle. Proc. R. Soc. B 160,
437-441.
RozSA, G., SZENT-GYORGYI, A. & WYCKOFF, R. W. G. (1950). The fine structure of
myofibrils. Expi Cell Re8. 1, 194-205.
RUDEL, R. & TAYLOR, S. R. (1971). Striated muscle fibers: facilitation of contraction
at short lengths by caffeine. Science, N.Y. 172, 387-388.
RUDEL, R. & TAYLOR, S. R. (1973). Aequorin luminescence during contraction of
amphibian skeletal muscle. J. Phy8iol. 233, 5-6 P.
SCHNEIDER, M. F. & CHANDLER, W. K. (1973). Voltage dependent charge movement
in skeletal muscle: a possible step in excitation-contraction coupling. Nature,
Lond. 242, 244-246.
SEIDEL, J. C. & GERGELY, J. (1973). Investigation of conformational changes in
spin-labeled myosin: implications for the molecular mechanism of muscle
contraction. Cold Spring Harb. Symp. quant. Biol. 37, 187-193.
SHIMOMURA, O., JOHNSON, F. H. & SAIGA, Y. (1962). Extraction, purification and
properties of aequorin, a bioluminescent protein from the luminous hydromedusan,
Aequorea. J. cell. comp. Phyajol. 59, 223-239.
SJOSTRAND, F. S. (1962). The connections between A- and I-band filaments in
striated frog muscle. J. Ultrastruc. Res. 7, 225-246.
SPENCER, M. & WORTHINGTON, C. R. (1960). A hypothesis of contraction in striated
muscle. Nature, Lond. 187, 388-391.
STEIGER, G. J., RUEGG, J. C., BOLDT, K. M., LUBBERS, D. W. & BREULL, W. (1973).
Changes in the polarization of tryptophan fluorescence in the actomyosin
system of working muscle fibers. Cold Spring Harb. Symp. quant. Biol. 37,
377-378.
STRAUB, F. B. (1943). Actin. Stud. Inst. med. Chem. Univ. Szeged (1942) 2, 3-15.
STRICKHOLM, A. (1962). Excitation currents and impedence of a small electrically
isolated area of the muscle cell surface. J. cell. comp. Physiol. 60, 149-167.
STRICKHOLM, A. (1966). Local sarcomere contraction in fast muscle fibres. Nature,
Lond. 212, 835-836.
SUGI, H. & OCHI, R. (1967). The mode of transverse spread of contraction initiated
by local activation in single frog muscle fibers. J. gen. Physiol. 50, 2167-2176.
SZENT-GYORGYI, A. (1943). Discussion. Stud. Int. med. Chem. Univ. Szeged (1941-2)
1, 67-71.
TAYLOR, E. W. (1972). Chemistry of muscle contraction. A. Rev. Biochem. 41,
577-616.
TAYLOR, S. R. & RUDEL, R. (1970). Striated muscle fibers: inactivation of contraction
induced by shortening. Science, N.Y. 167, 882-884.
TONOMURA, Y. (1972). Muscle Proteins, Muscle Contraction and Cation Transport.
Tokyo: University of Tokyo Press.
TONOMURA, Y. & WATANABE, S. (1952). Effect of adenosine triphosphate on the
light-scattering of actomyosin solution. Nature, Lond. 169, 112-113.
TONOMURA, Y., YAGI, K., Ku-Bo, S. & KITAGAWA, S. (1961). A molecular mechanism
of muscle contraction. J. Res. Inst. Catalysis, Hokkaido Univ. 9, 256-286.
ULLRICK, W. C. (1967). A theory of contraction for striated muscle. J. theor. Biol.
15, 53-69.
WALCOTT, B. & RIDGWAY, E. B. (1967). The ultrastructure of myosin-extracted
striated muscle fibers. Am. Zool. 7, 499-504.
WEBER, H. H. (1956). In Verhandlungen der Deutachen orthopadiachen Gesellachaft,
44th Congress, pp. 13-27. Stuttgart: Enke.
The Journal of Physiology, Vol. 243, NS o. 1 Plate 1
0
+
IA
_,-_i.
-
-Snat1
10 Jim
A. F. HUXLEY (Facing p. 43)

WEBER, H. H. (1958). The Motility of Mu8cle and CelI, pp. 33-36. Cambridge,
Mass.: Harvard University Press.
WILKIE, D. R. (1968). Heat work and phosphorylcreatine break-down in muscle.
J. Physiol. 195, 157-183.
WOHLISCH, E. (1940). Muskelphysiologie vom Standpunkt der kinetischen Theorie
der Hochelastizitat und der Entspannungshypothese des Kontr ktionsmechanis-
mus. Naturwuien9chaften 28, 305-312 and 326-335.
WOLEDGE, R. C. (1968). The energetics of tortoise muscle. J. Phy8iol. 197, 685-707.
Yu, L. C., DOWBEN, R. M. & KORNACKER, K. (1970). The molecular mechanism
of force generation in striated muscle. Proc. natn. Acad. Sci. U.S.A. 66, 1199-1205.
ZOBEL, C. R. & CARLSON, F. D. (1963). An electron microscopic investigation of
myosin and some of its aggregates. J. molec. Biol. 7, 78-89.
EXPLANATION OF PLATE
Active and passive shortening within a living isolated frog muscle fibre The fibre
is stimulated by a slowly increasing current; the cathode is near the edge of the
fibre which is seen near the bottom of each micrograph. The fibre does not give
action potentials in these responses.
The micrographs are single frames from a cine film taken through an interference
microscope (A. F. Huxley, 1952, 1954). The upper pair of pictures are taken with
the microscope adjusted so as to give positive contrast (dark indicates high refractive
index, i.e. A bands, Z lines and contraction bands are dark). For the contraction
shown in the lower pair of pictures, the microscope has been readjusted to give
negative. contrast (A bands, Z lines and contraction bands light).
In each pair of pictures, the left-hand one is before, and the right-hand one during,
the stimulus. The right-hand pictures show that during the shortening the myofibrils
near the depolarized surface of the fibre remain straight, and must therefore be
contracting actively, while the myofibrils nearer the centre of the fibre (upper part
of picture) are thrown into waves and must therefore be shortening passively. In
these passively shortened fibrils, the resting pattern of dark and light bands persists
(the A bands appear somewhat narrowed, but this is due to the obliquity of the
fibrils). In the actively contracting fibrils near the edge, however, the pattern has
changed to one with narrow dense lines. These are the C. contraction bands, placed
at the centre of the original A bands; on further shortening the Cz contraction
bands, at the position of the Z lines, appear as a second set of thin dense lines
midway between the successive C. bands.
From a film taken by A. F. Huxley and A. M. Gordon, 3 November 1961; cf.
Huxley & Gordon (1962).

The Journal of Physiology, Vol. 243, No. 1 Frontispiece: Huxley

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

The Journal of Physiology, Vol. 243, No. 1 Frontispiece: Huxley

Uploaded by

Copyright:

Available Formats

The Journal of Physiology, Vol. 243, No.

Activation of the contractile material

THE MECHANISM OF CONTRACTION

0 0.2 0.4 0.6 0-8 1.0

G The liberation of energy in the form of work plus heat (presumably

0 Length (%/) 50 100 150 200

01.00 2-00 3-00 4-0

K The isometric tension developed by muscle when tetanically stimu-

Text-fig. 4. Relation of striation pattern to the double system of inter-

-. 2-20-2 25 /4m (b+c)-*-

1.65 uim (a+z)

Text-fig. 5. Critical stages in the increase of filament overlap as a fibre

carried by the filaments would be appreciable when one is trying to

A. F. Huxley's 1957 theory

Text-fig. 6. Mechanism of contraction proposed by A. F. Huxley (1957).

kinetic theory leads exactly to the algebraic expressions fitted by Hill

Text-fig. 8. For legend see facing page.

TABLE 1. Phases of the transient response to sudden reduction of length

Phase 1 can be attributed to a more or less instantaneous elasticity in

Springs obeying Hooke's Law

Thin filament-.- Thin filament-

Text-fig. 11. a, diagram of active cross-bridges adapted from H. E. Huxley

wihn h yoi_ ha.Th_ latcelmn 0a

totetin fiamn irgd, an th,,pie oeettae lc

Texant-fg.12ra alternative to Fig. 11 b asha strucurabsis

A. F. HUXLEY (Facing p. 43)

You might also like