P ROG R E S S

I N BI OPH Y S IC S
A ND 8 I O V H Y SI C A L
(.,"HEMI & T RY

Editors
J. A. V. B U T L E R
Prot'cssor ol' Physical Chemistry
University of London
Institute of Cancer Research
Roval t ancer Hospital, London

B . It' A T Z
I'rolcssor ol Biophysics
t)epartment of Biophysics
University College, London

Institttt fiir I'hys!.>IoI;ische Che

clcr I.J»ivcl.sit it 1! Iiinchen
8000 Mih)rheo 1 8 - (t<)cthcstr'18e 8
'1'< lclon 08 11/89 43 21-22

A Pergamon Press Book

T HE M A C M IL L A N C O M P A N Y
N EW Y O R K

1957
 MUSCLE STRUCT UR E AN D T H E O R IES OF
CONTRACTION
zl. 7 ('. IXMxtey
(' OX 'I' I(' X Y 6
Page
I NTRODUC'I'IO)V 207

l. 8 ' I ' [ ( U CT U I tLr O l )' ' I'[110 MYOE1B[l Il . .

200
l. f n t erpretation of the striations 260
". ,'Itrncture of the A, I an d H b a n <La 261
f>[H< ussion of' the ovidoiico 206

l f. L r A R I I LI 'll K V I D F N C F O iV "I'fll' 1VI DT H O Y T H E A BA N D A N D I T S

COiMPOSITIOLV 266
I. Const ancy o f A b <LIL<I wr<llli 207
2. Localization of inyosin 270
3. The idea of sliding molecules 272

I I I. "<II(ff'I V A T I O N " AN D 'I' l l l)l 7i M V M B I I A N [)7 27'r

I. Tho l in k b e t woen excit s t i oti an<1 contraction 272
'. T l i o P~ fino 273
.'). Con t i n u i t y o f t l i o 7 i i < t c l i tb l ILrto 275
4. Mechanism of c o n d u c t iun a l ong 7~ntcrit[rrarteH 270
.). Loiigit u d i nal spread of act i v a t i ori 277
G. 'I'lro f'urictional u n i t' iii st r i a t ed r l u l s< I< 278
7(. Otln)r f u l i c t i o n s u f t l i o 7i [i ) to . 278

I V. A H Y P O T H E SI S V O[ t T H I ' M I : ( .'HANISAI OF C O N T f t A CT I O N 270

I. Statement of t l i o l i y p o t l iesis 281
M atlternatical form u l a t i o n 284
( ull l [ )ILI'IH()tl l v l't 0 I I l l . f . H I ) ([ IIILtl » I I H 287
(, ( » )i s o ( f t l()11(')I.H ()f l h <' f l y [ ) <it l l (!HIH 201
[.I . I . o n g t l l e t i i li g o f a H t i i l l i l l a t c<l )tins«l<' 201
I.2. I [ ) l i o n <l()rl Hl)ul't<'.I»rig ') 02
t .;). A c l i v a l i u r i a i » l n ) l o x o l i u t i ') 03
Siz» tlrr<l rlutnbor u [ < :or)(i'll(:ti()tr si t u s )06)
6). I. [(ange of rriover»r iit of' Hide-pieces. 29);
D istanc(. botwcoii Hucccssivo A s i t e s
. I,.[, S [ ) (L('llrgH I' x [ )('('t('(I ( ) » H ( I ' » ( ' t » l ' ll l g l ' ( » » l ( I H 20 (
(i. I ) I H <'IIHHI»rr )97

V. ( ) ' I'I I I ): I' I ' l i [ <'NOM I ): NA I iV [ r i U)S(11.10 209

I . I' Hl'Iy (.'hrlngoH I» IL t,wit( )i 300
I. I. I , a t oircy r o lax u t i ori 300
1.2. 1ncrease iii torsional rigidity 301
1.3. The "alpha process" 302
 M IJSCJ,J: s ' I ' I < I' ( ,"I' I) I< >: h N I ) 1 ' l l K » I ,' I I ; s » I' (' » N 'I ' l l h < " I ' t r ) N

1.4. Lrarly decrease of extensibility 302

J.S. Early heat liberation 303
1.<i. General discussion of early changes 304
2. Decreased extractability of p r oteins 304 MUSCLE STRUCTUR E AN D T H E O R IES OF
3. Optical changes during a twitch :) 00
3.1. S(,attering of light :J0;)
CONTRACTION
3.2. Decrease of birefringenr < :I0<i
4. Tetanus tension :I<><i .'I. E. 1Iu;t;ley
4.1. Absolute valnes ,'I0<i
4.2. Th o h n n l t o s h u l'<(.'nnlg nl a t l ' I anus :I OS
I N T Jto D It CTJO N
Distribution of other substances ;<OS
S).1. Sarcoplasmic proteins 308 l t fras see»re(l natural t» al l wh o h ave studied v o l unt ary m u scle wit h
S).2. Uttra-vdotet absorbing )no<,m ial ;I00 tire r»icroscope to suppose that t ire striations are an import ant c lue t o
t ,he»rechanism of cont r action . U n t i l t h e e a rly y e ars of t h i s centu r y ,
V l. CONCl.llill ONS ;it »
they were almost th e o nl y c l ue, apart f r o m t h e p r o cess of shortening
or t.ensiorl developrne»t itself, and int erest was accordingly centred on
t he changes that t h e s t r i a t i ons undergo d u r in g c o nt r action . B u t n o
c oherent th eory o f c o n t r a ction emerged from t h ese studies; p e r h a p s
i t is for t hi s reason that t h e h a r d -won k n o wledge of m uscle structur e
fell into neglect as rapid progress began to be made in muscle chemistry
«nd in the energetics of contraction.
Up to the outbreak of the second war, these branches of muscle
p hysiology were able t» 1>roceed successfufly w i t h ou t r e ference to t h e
d etails of s t r u c t u re . I t a p p e ars no w t h a t t h e d i s coveries tha t w e r e
I<lade in rrruscle biochemistry u p t o 1 9 3 9 w er e r elevant t o r e c overy
processes rather. than to th e contraction mechanism itself. T h i s is not
t,o belittle their importance: f rom the point of view of muscle physiology
tfrey led to the discovery of AT P an d t o t h e idea that t his substance is
the imr»ediate source of' energy fo r c o n t r a ct ion, w h il e i n a b r o a d er
c ontext they laid the fo«ndati»rrs of our understanding of the glycolyti c
c ycle and. of t h e w a y s i n w l r i c h e n ergy i s m a d e a v a i l able f o r t h e
;Lctivities of al l k i n d s of c ells. I t d o e s h o wever mean t ha t t h ese dis-
c overies had l i t t l e i n u n ediate r elevance t o t h e p r o b lem o f h o w t h e
c»trtr;Lcti»tr i t self i s f » x>ugftt, ;Lbout ; c o t >versely t h e c h a r a cteristic
features of' musclestrueture were irrelevatrt to the processes that were
bci»g (:htcirf;Lt,(;rf. 'I'itis f>»sit,io» wns brought to an end by the discovery
» f th(' Irrt('I')Lett»trs» f »I y » s » r IL ) r d A I ~ V ) ILrl(I »f. tfre col» p o sit)B liat)ul'e
»f' "l»y<>sir>." I tc o « frl l>e s;Li(f t,h;Lt,
muscle chemistry had then become
ripe fori»tegration with i»formatiotr about structure, but in the mea»-
tir»c; the ktI(>wfedge tlrat i )art bec» gaine<l by t h e n i n eteenth-century
»ricroscopists had beer< largely forgotten. T h i s is illustrated for example
)>y comparing tire brief acco«nts of the striations, and of their changes
d uring contraction, t l r a t ; Lrc t o b e f o un d i n m o d ern t e x t - books, wi t h
tire f»11 and accurate description in say t h e 1 888 edition o f M I OHAEL
I"(>s rFIL's text-book.
The chemistry of th e muscle proteins did indeed retain some contact
»(
 M USc n '15 STRiTUTl >B Z A N I > I . "H z o R I I < s < ) I ) c < )N ~l R A U T i oN
with microscopical information; for example Nor,L and Wzszz {1934)
showed that the birefringence of the 2 bands could be accounted for
by the birefringence of "myosin" threads. This contact seems to have
been lost at the time when it might have been most fruitful; t h ere
was no attempt t o l ocate myosin proper and actin with respect to
the striations until more than a decade after the separation of these
proteins.
Knowledge ofthe mechanics and heat production of muscle reached
a stage at which they were ready to link up with other lines of informa-
tion on the contractile process in 1938, when A. V. Ho.z, published his
well-known analysis of the relations between tension, speed of shorten-
ing, and heat p r o d u cti on . H o w e v er, i n s p it e of H n . L's repeated calls
for chemical studies to parallel his analysis of the time course of energy
liberation, this work remained isolated until the recent demonstration
by F m c x z N s TziN et <Ll. (1954) and Mo MMAzRTs (1954) t hat t h e
amounts ofATP and creatine phosphate in a muscle do not falldurinigr
the contractionphase of a twitch.
As regards the processes by which the contractile mechanism is
"turned on," itwas clear by the end of the war (KUzzLzR, 1946;
KATz, 1950) that the reduction of the resting potential which occurs
on oxcitation is th o nor i iial st i m u lus for contr;Lction, and a n u rnbor ol'
physical changes were known to begin during the "latent period"
between excitation and the development of tension or shortening (see
pp. 300 — 304).
Although th e b asic facts concerning the st ri at ions, which had b een
known for 80-100 yearn, were unduly neglected at this time, it must be
admitted that ou r k n o w ledge of m u scle structure had not m ade niucli
progress since the turn of the century, and in relation to the available
techniques it was less advanced than other branches of muscle physio-
logy. Even the application of the electron microscope did little at first
beyond confirming (and restoring to respectability) the picture that
had been handed down by thenineteeth-century rnicroscopists; i»dec<i,
s everal of t h e ne w c o nclusions that w er e d r awn f r o m t h e e a rly w o r k
with th e electron m i c roscope have since ti n ned oiit t o b e u ) i f'o»)id<)<t.
.l5llt l i ). till($ hLst f< lw $ < ))if)< )1 Ill<Ill))<)I'<)t l f » / ) <)I'tiL)lt p < )it)ts ) Ll)<)»l i l l
s triations theniselves, and about t h e spatial di st ri but ion of t h e s t r » c -
tiir'ILl p)'otoi)is, l)ILvo c<)inc <)iit, ainl;Ls L I'<;s»lt it Is n<)w possil))o to Inak<;
7
ststeill e)it s a b o » l ' t l ) c 11 )t1)YII'lt<) sti'li<)tiII'<) <){ i)ills<:l<)w l)il l ) ,LI'<) s<IAI .
«iently d e t a i le d t o h a v e a be a r i i i g u n t he i i i t e r p r et ation ot' t li<'.
mechanical, thermal and chemical events. I t r e mains for the fut»ie
to decide how far. the views that l ani adopting here about the structure
of muscle are correct, but I d o no t t h i n k t h a t t h ey are any m ore likely
to be in error than are the current statements of its mechanical and
chemical behaviour.
I N T 1L 0 I') U C T I 0 N
Up to now, thetheories of muscle contraction that have been put
forward have often been based on only a singleaspect of muscular
activity. The lactic-acid. theory, which might be classi6ed as primarily
chemical,did indeed take account of what was then known of heat
productionand work done by the muscle. But As Tz URT's (1947) theory
was purely structural and. RAMszx's (1944) takes account of little except
the energetics of contraction, while most of the other recent theories are
chemical and make no attempt to accommodate eitherthe relation-
ships which Her. found to govern the release of energy as heat and work,
or the known features of structure. Por,xssAR's theory (19Ma,b,c,d) is
very comprehensive as regards inechanical and thermal data, and could
probably accommodate the known chemical events,but it takes no
account of muscle structure and it does not fit with some of the impor-
tant facts about heat production {WD.Krz, 1954).
These theories have done good service by suggesting lines for further
work and.by bringing together observations from more or less diverse
Belds. Their onesidedness has been a natural consequence of the fact
that the different branches of muscle physiology had hardly made
contact with one another; this did mean however that there was little
chance thata generally satisfying theory would.be produced. But this
is no longer the position; it should by this stage be possible to produce
hypotheses which try toaccount simultaneously for the mechanical,
thermal, chemicaland structural changes which are known to occur
<luring contraction. Later in this article I shall try to make good this
statement by puttingforward a,hypothesis which does this to some
extent. I t a c h ieves a f air a greement wit h o bservation in several
respects,but I do not suppose it is by any means the only scheme
that could be devised at the present day with an equal degree of
Sl)CCBSS.
Much of the new evidence on muscle structure has been recently
reviewed (Pz)LRv, 195. ); HANsoN and H. E<. HUxrz Y, 1955) and. I shall
tl)erefore give only a short account of it h ere. T his forms the Rrst
section of the article, while the second reviews oMer observations and.
opinions in the light of this work. The third section deals with activa-
<'. ti<))L an<i the function of t h e g m e m b r a ne ; i n t h e f o u r t h , t h ere is an
;Lccount of the hypothesis to which I h ave just referred, and. in the
(ill) are discussed various phenomena for which fresh interpretations
:Li
<.s»ggested by the structuia1 data,.
' A)e a)ticlc m akes no a t t e n ip t a t c o m p l eteness as a review, and i t
co)it Line a higher proportion of historical matter and of speculation
than is customary in review articles. I t d eals mostly with structure
:Lnd witli the physical changes that accompany contraction, while the
cheinical and electrical events are referred to only in so far as they have
a direct bearing on these central topics.
259
 M(TSC T Z H' 1 ')I IT <"'I'TTTL'1: r( N 1) '1'11 ii; 01(1 ii: 8 () Ii' C ON '1'I(ACTION
I, t.>TRUOTURE o F T H E M Y o i 'I B R I L
I. 1. In t e rI)r statt'o)L fothe strt'(Ltt'orts
T he essential f a ct s about t h e s t r u c t ur e o f a s t r i a ted m u scle fi bre a t
rest that w ere established by th e ni neteenth-century m i c roscopists are
the following.
(1) The transversely striated appearance of a f i bre examined in
ordinary l i gh t i s d u e t o a n a l t e r n at ion o f z o nes of h i g her >and lower
refractive index.
(2) The interior of the fibre consists of fibrils embedded. in a varying
amount of probably liquid sarcoplasni, which also contains nuclei and
granules. % hen th e fibrils are separated from one another, each shows
the banding pattern characteristic of the whole libre.
(3) The zones of higher refractive index (Q or A b ands) are bire-
fringent (uniaxial, with the optic axis parallel to the length of the fibre,
a nd wit h p o s it iv e sign), w h ile t h e z ones of l o wer r e fr a( t iv e i n dex ( J
or I bands) are optically isotropic or nearly so.
(4) Each I ba nd is b isected by a n a rrow line of h igh r efractive
index, which appears to represent a more or less continuous membrane
stretching across the fibre and at t a ched to t li e sarcolemma.
( 6) Thc c e n t ) no of t l ) e A b a n d s o metimes h )LH a, lower r (:I');L(:tiv<1
index than theedges, and isthen called the H band.
These points were first clearly stated by BowMyLN (1840) for ( I) a»d
(2), HRi'TOKE( I 86)8 ) for (3), Doui i.' (1849) a»d l<R+()s)." (1869) for (4), aiul
HENBEN (1869) and E NGELMANN (1873a) for (6). T hey were clearly
understood by ENozLILL> NN, P oLLE TT, and others who investigated fresh
f ibres by visual microscopy towards the end of the last century, but t h c
first has bocii ; L source of i » uch co»fusioii i n » ) or e reco»t t i » i es. 'I'ho
striations do not defer appreciably in the absorption of light; c onse-
quc»tly tlicy arc invisible if thc fibre is exai»ined iii ordinary light witli
a wide condenser aperture. T h e r e f ractive index diff'erence betweeii A
<L»(I I (H L» I ) O » > cL(IO to iHII()W I)I) I)y H 'lr()()I)»lg ( I < )W» lr ll(' ( >()»(l(t»H( 1': I l l ( 1
striations then become visible b»t the appearance depends o» tlie
foci)si»g>' <>f tl)c T))ic)'<>HO<>p('. 'll' it is f<><1»H(>(I rx;L<;tly <>i> a thi» i>,L) I, <>I;1,
Iil)T<;r iLI»l<)Hlr»()ti l l » g ) H HO(',»i il lrl>(', »11(11'<>H(><)I)O t»I)O 1H 1')LiH(ul iHI)gyl>lrly,
I)igl) r<:Iraot) v ( » ) <lox I' cgio»H)LI)p a)' I)rlgl>t l ) l i t l l t l l ( lr u b o is l o w ( )I'((I
t l)o ii»agc is 1'<ivc)'H«<l:L»<II) igl) rcl'i acti v(1 i»(lcx rogi<)»s bcco)ne d;L) I(, '.I'o
speak of t li e " <Iarl' " : ) »<I " I igl)t " l m » d s is t l )(>rofo)r » ) r )Lni))glrss 1»>I(HH
t lie position of fo«us of the niicroscopo is specilied; in the last cciitury it
became customary to use the low position ("tiefe Einstellung"), so that
A and 8 c o u l d b e c a lled d a rk ; i t i s c o i i v eiiient b u t ; L lso pol r r i l i a l ly
misleading that t h i s agrees with th c appearance of' it l ibre stained witl >
the commonly used basicdyes. The interpretation of the image of a
"phase object" such as this, in which light is retarded but not absorbed,
260
S TR U C T U R E O F T H E M Y O F IB R I L
became less important with the improvement of section-cutting and
staining methods, and it seems nowadays not to be universally under-
stood even bythose who work with the microscope. The interpretation
is still more difficult in a thick specimen such as a frog muscle 6bre, and
it is very difficult to tell, for example, whether the dark bands seen by
8UOHTHAL et (Ll. (1936) were in fact the A b a nds as these authors
assuiiied.
I. 2. Strttcturs of the A, I urtd H bands
It was widely supposed before the second war that the high refractive
index and birefringence ofthe A bands were due to the presence there
in a more or less solid state of the "myosin" which can be extracted by
s trong salt s o l u t i on s o r d i l u t e a c id s ( K 1THNE, 1864; D ~ I Lz w s K Y ,
1881). Although this view was strongly supported, by the quantitative
work of NoI.I, and WEBER (1934), it seems to have been discarded after
the war, partly because the "myosin" had, by then been shown not to
be a single substance, but chiefly, I t hink, because it was diKcult to
reconcile this localization of what was thought to be the contractile
reyae~in Actin I a ' t) ' I sarlament
f ilament f ila m e n t
I» ig. l. Diagram showing the arrangement of the filaments, within s myof ibril,
which has been suggested by recentobservations desoribed in the text. The
<Jcgr<>e of stretch corresponds to the extended length in the body. T r s r(averse
dimensions sre enormously exaggerated in comysrison with longitudinal ones.
g'hen the length of the muscle is changed, the actin and myosin Bilaments slide
liest one another in each of the zones where they overlay, snd only the 8-
filaments arc actually stretched or shortened.
Hubstance with the current idea that contraction was produced by the
I 'ol(li»gy of' protein chai)is that c x t en<led throughout t h e l e ngth o f t h e
»i«H«Jo. Becently, good evidence has appeared. that these charac-
t o) IHi,ics of I ho A b Lud aro iiuleod due largely to t h e localization t h er e
of tI)(', myosin (as opposed to actin ) component of the old "myosin."
Ai tb( sa»)e tir»e, observations on the changes of the striations during
s tretch a n d c o n t r a c t i on , )Lxul e lectron m i c r o scope s t u d ies o f t h i n
sections of muscle, led to ideas on the structure of the myofibril that
lit i)i well with a localization of the chief materials of the fibril in ddferent
parts of the syste)n of striations.
The resulting picture of the structure of a 6bril is shown schematically
in Fig. 1. The main features of this were arrived at independently by
261
 h11!s()T 'I. RT IL(r(!'I'Ir lt z ) < N » T » 1 1 « II I IIN « Y < ' « N ' I 'IC I ("I' I «V
H . E. H v x r,z Y and H)iz soz ( 1054) and by A. 1<'. HI)xi.z Y and ¹ z i ) z i ( -
ozRKz (1954), although more of its de tails a re due to t he former t h a n
to the latter au t h ors. F i g . 1 i s in f act a l m ost th e same as the corres-
ponding diagram of HazsoN and H. E. Hvxz,zY (1955). Most ofthe
evidence on which this scheme is based has been thoroughly reviewed
by Hx z so N and H . E . H v x z z Y ( 1 9 55) : I s h a l l t h e refore do no i»<)rc
than summarize it h ere.
T he essentials of the scheme sliow» in .Vig. I L ( e ;
(1) The A b a n d o wes its high r efractive i»d e x ; L»(I. its biret'I i»g(.»c(
to a set of rods or filaments arranged alongside oue a»other. The
length of each of the rods is constant at about 1 5 p so long as the muscle
does not shorten enough to bring the ends of the rods into contact
with the Z lines.
(2) A second set of filaments extend from the Z line through the I
and into the end of A , as far as the beginning of the less dense H
region. These keep a constant length of about 1 0 p so long as the
muscle does not shorten to a sarcomere length below 2 p.
(8) When t h e m u scle lengthens or shortens, the f i l aments of t h e se
two types slide past one another.
(4) When the fibre shorteus so much that the I filaments of the two
e n<is of <»ic sarc<)merc come i n t o c o i i t a ci , t h e y s l i o r tc u f u r t he r b y
folding or crumpling near the point where they have come into contact,
and possibly at other places. Similarly, the A. rods may fold at their ends
if the fibre sliortens so much that they come into c<)ntact with the Z Ii»c.
(5) Myosin is a principal constituent of the A rodlets, a)id actin of
the I fil a m e nts.
(6) Corresponding I fil a ments of the two ends of a sarcomere are
joined by a very ex t ensible connection, the 8 filament.
(7) In transverse section, the filaments are arranged as shown in
Fig. 2.
The chief points of the evidence which led to this picture being put
forward are asfollows:
(1) L<'xistsnce o f ttr)o sets of f ilaments. ".I'he two sets ol.' Iilainents ai e
bea<ltit'»IIy sliow)i iii t l i c r «gioi). of tl)c ; I b ( L»(I wlicrc t I)ey overlap, itl
<)I(l<'I I'(»I » » c l '<)gi'!< I)I)s <)f I)»{ill l <)»g l t » ( I » »LI )L»<I { I')L»sYOI'is<' sc(!l 1«lbs <)I
II'og a»(1 r<LI)bit »illsclc (IJ. I'~. Il ( ! x l ) I'Iv ) I!)5).ja ).
(2) Consfrtnr;y of length rrf A-brinell rr)rtlr.ts. (a) A. &'. HIrxr I:v ail(I
)
5 lzi) I )iRozRv it (195)4) sliowcd tl»Lt, in'l L Iivi»« isolateil muscle libre fr <»»
tl)e fi'og, pliut<)graphed witII ai i i n t e r f ere»«e » i i<;Ioscope, tlie A b i)»»I
s tays of c o u stant w i d t h , w i t h i n t h e e r r or s o f » i e asurement, d u r i n g
stretcli, passive shurteuiug aiul quick a»d slow coiitractious, so long as
the sarcomere'length does not fallbelow 1.!j— 2 p . They also found the
Hanic 111 l)assi v(. 'st I'( ticli IL»(l 1'el<Lx(Ltio)1 Usiilg I)ola i'Ized I(gilt (Ulll)ublished;
see p. 266).
S rR(r(,"r<rRI; « I r irHi t I e V O r ! r I L R r X,
(I)) H. E. H v x LzY and H<izsoz (1954) similarly found, by phase
contrast microscopy that th e width of t h e A b a nds of fibrils from
glycerinated. muscle is independent of sarcomere length, in stretch and
in contraction induced. by ATP treatment, so long as the sarcomere
length did not fall below 1 7 p.
(c) Hs.RM)LN (1954) recorded spontaneous contraction and relaxation
of isolated fibrils by cine photography with the phase microscope, and
• 0 0
0
® 0 0
e o • 0
0
)
I
I
cI
~ 4 4 OA N
I)'ig. 2. 1)iagraru sho<ving tho crraugement of the filaments in a cross-section
through the outerpart of an A band, )vhere both myosin {larger)and actin
{smaller) e)laments are present. The dimensions given are appropriate for a
muscle at its extended length in the body.
found that shortening took place by approximation of the A b ands,
with obliteration of the I bands.
(3) Constancy of length of I f'Lkrnzsnts. The gap between the I f il a -
ments belonging to the two ends of any one sarcomere shows up as the
H band in the intact fibril, and as an almost completely empty region
when the A fi laments have been dissolved away. In both cases the gap
inci eases in width as the fibre is stretched (H. E. H v x L z Y and H<!LxsoN,
, 1954), and the length of the filaments that remain after extraction of
t,hc A filaments is independent of the degree of stretch (H )LlvsoN and
.II, .I<'..IIvxzz Y, 1955, p. 247). In living muscles under the interference
uiicroscope, the H zone is conspicuous only when the fibre is moderately
stretched (neither shortened not g r eatly s t r etched), as would' be
c xl)ected. on t h i s p i c t u re , b u t t h e o p t i c a l c o n d i t i on s ar e n o t g o o d
« »ough to measure its wid t h .
(4) Constancy of X-ray spacings. The 415 A period of the low-angle
X-ray diagram was found by H . E . H v x r ,zY (1952, 1958b) to be
unchanged when the muscle was stretched. A spacing ofabout this
value is seen in both A and I ba n ds under the electron microscope
(Her.r,, J<LKvs and SoHMrTT, 1946; DRmzR and Houaz, 1949), so it is
268
 I>r U H (", 1 I'! H 'I' lt I' (' ' I' I' IL I: A r N Ir ' I' » I: ( r I> I I. 'H ( r I ' ('( I iN 'I' lt A ( ''I' I (>

riot clear wl>etliev tlic X - r ,LL obs<u v;Lti<»i is rc;LIIL pvidciicc f<>i (or>st;Lr><:1
of length in t h e 2 o r t h e / f i l a ments, <>v l>otli. T l i e l i i g li-;L»gle X-r«LL
pattern also n p p cnrs t o b e l i t t l e a f f ected b y s t r e t cl> o> contvnctio»
(ASTBURYr 1!)47 ).
(5) JOCertiO>Lf O Wry/OS>'>L it):f , «O>(l «C/i)), t')), /, fil«)))eit/s. HA H H L ).r)A('1I
( f053) arr(l H ANsoN nncl H . Lr'. H c/xr,f:1- (I!f53) f'ound t ha t s o l u t i o ns
k nown to d i ssolve niyosi» would r e adily i cc i>u>ve i»ost o f t l i p . 0 b n i u l
fror>L fibrils of r a b bi t m u s cle ; t h e c<»rtrnl p;>I t of t h p , d b a n<i clisnp-
peared only on p r o l onged ext r act,ion. H A s sr.'r,«A(.fr showed by v i s co-
sit»etry tl>;Lt the » i a t c r ial t hnt w ent i i it o Holut ioii was about ! );> pc>' ('(rrt
myosin and 5 per cent actin . T h e l r e g i ons of' the fibrils are »o t much
ILffccted by t l >is ext r a ct i o n , ; L»d t l >C,.I regin>t is >cd>ice<i to t,l>p H;Li»c
<tensity as th c I ( e x c ept t l >nt, if' th c f i b t i l i s Htifiicicntly c x t c n dc<l !o
PoHHPHH I'I 4> L»tlsr t h P S C 4C Co»lc <Lltllos fr (',i>1Ptrr'<Lf ter' the c' x t l '<Lct tot>).
r
The f'act tf>at the nctiii is knowrt to be present in ri»tveatecl fibrils nmkes ;I Ir> Ir
i t pr o bable t l >at t h e r e m a i ning fi l n »rents coi>sistP<f lavgcly o f ; t c t i » :
this was confit»>cd by H ANHoN:Lt><l II. Ir',. Huxf,i:v ( I !!55), >vli<> Hli<>tv<><[
tliat t he y d i s a ppp Lvcd orr tre tt>t>cr>t, wit li a Holut iot> kin)rvt> to (lissolvp
nCtltl .
(ti) J>eh((<riot()' o/' Ji/(t»)r t)ls «/ s/ ) o>'/. s«)'('o)))(r'c./e))!///>s. =>(t Ht>1'coi»('I'(
I<',t>gtrhs I>(:trw<".(,t>;Lint>t, I ( i ; L i i( l 2 ( ) l r , 1 4 (> .' I l>;L»<I 1'c'1;L>i>H >ts r)t'd>»;>I 1 I'rrl:r r rrr r I lrr.lr l nr';
I r l r rr< rrrrrrr nr >fr)>i rrl t )rr' r'rlr "r' rrf rrrr r i r rlrrtr'rf l r v r rrg
length of I 5 lr, but the l fi f o »tents nrp too lori« to clo this. 'f'hey appp;Li Ill<>it lr f i l m Vn r r r r t l r r I ' r < >«, rrrr it rrrrrrf rtr rl. Ir r r tlrt: > ro r ' or»tr<ors >trot>: b r ><'Ic-
nrrrrrrl ; r rr<f I lr r r rrli r l ; rr I', . I l r r rrrli I » i r rlrt. I r /): r r rrrrfrr r)H rtr <I so;ri t o r > »r>fcc
to HI>et t<»1 by I<>c;Llizc<l l<>lclirtg 1L>rd not by 1<nifi>t tli. coiit>1>ctioii r H incp . I I rrrrrrli ; > fr) rr rr) <I rr'I : I r r r ' l<rrn»rrr<l rrrrrf I I >; r rrrli t r r ' i « l r t . 'I'frn'(' <fr'gr'('oi of
111>l'1'ow (ferlse 4>LI>ds nppc<11', plLrticular'ly 'Lt t h ( : ceittte o f ' f l i c . 3 b >L>1(l ;rn .i l rrrrrrr, I trr i ; r r r rrrrrr n I r rr)(fir rr r r rrr Ir r r>ir Ir r rrrr( rrrrfrr",>tr'<I to t f r rr
Ir f'r rrf' I lrr f r l r rrf rrr r':> I rlrro 'I'lrr rr'irll
fr rrt'Ifrr' .I Irrrrrrfi ii ir'r'rr trr Irr' rrrrrrfr(>nf(r'rI
wl>eic: tlic <»><la of L d j;Lccrtt I f i l >Ltncnts i » oct,(IL I '. . H i ' x f . t : v ; > tul
rr lrilr I lrr I Ir r r r rli i r r r n; r . r i > > o rrft Il 'ri I Ilr' Iil>n i i i t n t r I « r l . Ly > t r ' r i r n r r rori i r r rr
H AlvsoN, I ! ) 5 f : A . fr ' . H t rxl.f:1.' nrid N l z r r f : I t(.'I,'itic I;, I ! )5>4
) . t ) t t stil l r rlrjr r > i<'r', l l . ; I() in r : r 'rr r l r l r ' l r i r ' I ' >I)it' I 't Ill'r' l i r r r it r <I l r r rr i r t rrrrr< <>'lrrrsr' si rlrr
f'urther short(;r>i»g, tlie clpiise bands nt the Z l i nps bcconle cx t>«gc1'ntp(l < Irrr;> fir I <rr I lrr';) i i i rrl' I lrr fi l m') )orr r;rrr rro. <rf'(> -1 I. I''nrrrr rr oirrr tilrrr toto n irr
ns "cor>tvitction 4;L>1(ls," Lvlticlt c»L>r 11>Lt iivally bp i » t et pre.t(d as clue' 1<> r rrll:rlrrrr;rt irrrr <r i<fr l)r. IC. I'X 'I'.c> r,rrn.

f oilin g o f t h e e t><Is of t h ( ; , 4 f i l a tn<uits w l l('1'c th('v rn(.pt t h(' 8 Il l >(

pi'0 pe 1'.
(7) l<'.visle)r<'r o/' >'>' /i/re)))<'))ls. H . I': . ll ( ' x i , i : v ; > , i>d H L NH(>x ( I!)5>-f:
HANS»N »»d I I . I ' . I I Ir x),I,'v, ! <)5>5>) fot»>(l t h>L1 I> Iibt il I'i <>t» wlii< 4 t Ii<
~f-baird r>t;Lteri;LI liacl;Lil becir clissolvccl ;>w;Ly coiild Stil l 4 P Hti ctc. Ii«l.
leavirrg aii npp Lvctrtly cinpt y « a p ; Lt t lie iiiiclcllP c>f' e>Lch H,t> c<»»ei(,;>>><i
wr>iil<I alt<>i t<.»;>g >i>i I » s s i v < ly L v l>(r>i i(;I<.;>H( <I. 'I'I>< > c >itiist 1 I >< t'< I'<» <
1>c H<»iic l» g l i l y c x f c t i s >blc c r »»>c<rf ir»is I>( I w« » 1 l i ( I Ii ll t » l ( ' » ! i r r l I I > (
1wo en<la c>f';L»y c>r>c; Hai pot»eric.
l ) 'I'I"I'« I)(/(I))r'))I 0/ ll )(' /t l ((>))('rl/s. I 4 ( ' r » 'I'rt I lg('ill ('I it ; t l >o>vll I » I' > <r .
(N
>H fr>Lk('» I >'I I»> I I . Irr. I I < r X I I'; v H ( I!I;r'I >) rr< t y Ir<.:><if>Ii>I <'I< (rt i'<>i>
gtiiplis o f ' t I;L»H< crse Hectiorrs of.' ritb b i t ; L r i(l f i o g r » u i s c l (.. T o 1 L l t>l'r'(
CX!Crit, tl>is (L1'I'ILI>gc'»1(>n't w>LH Huggcst(>(I. by I he s>L»1(' n tltllot.' s lorv-l>»<'I(>
5-Vay ObneVV;Lti<>»H (I!)5 ), I!)5,'Ib ). LVIiieh ; >>1 i>IHO thc. SO>iiCC. I'<» f h <r
( I i t i) (r t) Hint) H.

Fig. 4. Short«ning of a single I ba nd indn««d hy <1<>polsrising a small sr('s, of
<ho nlcnlbl'ane with B. mi«roplp<'I t>«(tip d>anl(>t>'I' 4 /< j In <'outa«t, wlfh th « i l l »'<'
surfa«o (i ls ; r i p <>I' lh« p i p « i t « i s n<>i w«ll sh<>wn in i ,his r< prod»(<i,i<»>l. 'I'w<>
su«<(<>ssiv<( I'r>n<»<s f'r<»» » <i »<> filo>, Il l I' r < »>s /s«.;
s ri r f I<I,ju s t, I >< f<>r<, <n><l
tsft, just s f t « r, t i n ; st<ar1 of' », n(>got iv<; I»ds«»ppli<sl I<> tls> pip«it«. .fsolat< <I
fil>ro fr<»n iho f r og ; I >olarisod light,, <s>mpensat«<I so tlu>t 2 b o n d s a p pear
dark; o t h e r o p t i cal conditions as in I<'ig. 3. l i e f >roduce<l by permission of'
th(>.lour>1«l, of 1'Itis>'olo~pg fro)n A. E, H ( > x>.I<v on<i TAYLOI<, I!l.)S>b.
I I I t . t > < >I> f l i t J g YOI> l l t f y l f >
l. 3. Df w ;<4saioit, ot'the et)tdence
This evidence appears s ufficient t o s h o w t h a t t h e s c h em e u n d e r
discussion is correct at least in its main outlines. There are obvious
deficiencies however: for instance, isolated fibrils contain tropomyosin
a nd at least one unknown pr otein as well as actin and m y osin (Pz z z Y ,
1953), and the material at th e centre of the A fi l aments evidently
differs in some way from that composing Che ends which are easily
renioved. by fluids which dissolve myosin. Points of this kind. do not
however alter the main thesis that changes of length involve two sets
of filaments,one composed largely of myosin and. the other largely of
actin sl i d ing past one another
Some of theimportant points in this evidence have however been
recently questioned. H ODOE (1M5) has published some extremely
clear electron micrographs of dipteran flight muscle in cross-section
which show only asingle set of 61aments in the A bands. He regards
this as contradicting H. K. H Uxf.zY's (1958a ) evidence for a double
set, but it seems unsafe to deny the existence of a structure on the
grounds that it has not been seen in a particular preparation treated in
a particular way. The fnaterial and, the treatment are both very
< lifl'crcn(, from H . I <> . Hit x r. I: Y's, Bn<1 it w o ul d b e m o s t v a l u a ble t o
discover what is the reason for the difference between their electron
m icroscope pictures. Aclue may perhaps be given by the fact that in
h is X -ray s t u d ies H . Z . H Ux i d<,
Y found. evidence of the secondary
f ilaments only in muscle that was in rigor, not in f r esh muscle. H o n f i z
also claims that his longitudinal sections show that the 61aments of the
A and.I bands are continuous with one another. Apart from the fact
that his I bands are not well preservedand the continuity is not easy to
trace, at any rate in the published reproductions of his micrographs,
this is again negative evidence in that 61aments originally separate
miglit become adherent d u r in g t h e p r e p aration . I t i s c l 'ear however
Cltat these points need further investigation.
Another criticism of the evidence presented here concerns the inter-
fi~f>Oft<,'c fillet'oscope <>1)>t<>l'vattofis o f A . I <'. Hl ) x f . tr Y a)id NI E D E BGEEKE
() 05>4). BtfonvffAD et al. (1<NO) found, on isolated frog fibres under the
ordinary light microscope, that the A band appeared to be more
extensible than the I, wh ich is the reverse of the 6ndings reviewed
above. A s m e i i t i oned oii p . 2 01, measurements of this kind on a thi ck
specimen like a frog fibre (approx. 100 /4 diameter) in ordinary light are
not reliable; t h i s wa s th e r eason for d eveloping the i nterference
i nicroscope used by A . I < H U x L EY and N I E Dzz o z z KE . B u t C ~ r szz
and I<)fAri Eis {1055) now claim to have substantiated this result using
polarized light, with which it is ceitainly possible to obtain a much more
trustworthy image than withordinary light. They agree that in fi xed
205
 M (7S(<Ji ( i. Q P n(J (< rP Jf JQJF~ A >< (> rP(( (P<> J(( ><S (> >< ( <(>>< q~>i A(arP( <> ><
or glycerol-extracted material the A band appears to stay of constant
width, but st ate that in f r esh isolated fibres from the frog the birefrin-
gent regions increase in wi dt h d u r i n g str etch m ore t ha n t h e i sotropic
bands. If this was true, it would invalidate much of the evidence I have
q uoted. B u t N I E DERGEEI<z and I a l s o used polarized light o n l i v i n g
fibres on several occasions,and found the A band width to be indepen-
dent of t h e d e g ree o'f stretch, j u s t a s w e d i d w i t h t h e i n t e r f erence
microscope; Dr. R. E. TAvLoz and I have confirmed this again since
the appearance of CAELszN and KNAPPzls's paper. A series ofphofo-
micrographs showing theconstancy of width of the birefringent band
is shown in Fig. 3. T here is therefore a direct disagreement bef,ween
CAELSEN and KNAPPzrs's results and our o wn ; i t i s i m p ossible to say
what is the cause of the discrepancy, since CAELszN and KNAPPEJs
do not state the conditions under which t h eir observations were made
(numerical aperture of objective and of illuminating cone; whether
c ompensation wa s u sed o r n o t ; t hi c k n ess of s p eciinen) an d d o n o t
publish any of their photographs. It is possible that they used too low
a condenser aperture; I have found with frog fibres of ordinary thick-
ness that polarized light may then give an image almost indistinguish-
a ble from t h e o r d i n ar y l i g h t i m a g e . N J E D m GEEKE and I d i d n o t
publish any of our p olarized light results in 1954 because this metliod,
though better than methods using ordinary light, is less reliable than
the interference niethod for thick specimens.*
II. L < Ali LIL<z L~vll>L>NOL< oN TJJ. E WIDTl i o l < T i i'Lp A B A N D
AND IT S C O MPOSITION
Some of the evidence for th e i dea t hat f i l aments of actin an d m y o siii
s lide past onc another whc>i a Jnusclc cliangcs length was given in t i l e
last section. T his included only the recent evidence which actually
led to the idea being put forward. Several of thc separate points that
are established by t his evidence (e.g. constancy of A b a n d w i dt h,
prcscnco <>1' »>y<»>in it>. A 1><><i(ls} wcpc >clsoafcdly suggested,
w id offc«
c learly stated, b ot h i n t h e v o l u m i n ous li t erat ure of l ast cent ur y a n d
in moro Jcccnt work. I.'robably none of 1 l>is old evidence is important
a1 fl><> 1»oH<»>t <1:>y fi>p 1>o11>i»g 1~> <1<;<;i<I<> 1><>w 6>< 11>is i<le;<, is <u»roc(,,
but if is 1>cr l>al>s i>istrucf ivc 4> (:x;>>»1»(> su»ic ol' tl>i>J w<» k iu 1,1>c hope
of seeing how it came about, in thc first p1a,c(;, that the idea, we are
<' I' 'I»> <<><u«><>iH (J><><, <,J<
i»>l>liu«<> <'<>y>< i» (I><> (>h»><i<>J<J>i> l<» »7 <>xi«<>p (I«> fil><<> (r<>v<>r>«>
<> greater thi<.l«><>8< of »>us<>le substance than tho obli<Jue rays in the Plane PerPen<Jiculo<'
to the fibre; th e total retardation of the extr<><>rdi<><>ry comp<>nont by the parts <>f the
J11>ro which am ul>ov<><><> <1 1>olow < 1><>J>1<><><> <>f f<><>
<>J> J8 (J>or<>J'o<x) grooto<' for tJ>of'<» >nc<
than for tJ>e 1<>ttor g<'ouJ>sof rays. T h e c o r r esPonding orror w i t h t J ><> i»te<forono<>
»>icroH<;<>pa is <>Ji<ni<><>(,od Eiy <><Jdi<>z J>ro<,oi<> <o tJ><> immo<8ion fluid <>o <><> to t><i»g it,s
ref<<>ctive index close to the average w<>J«e for the fibr contents; t h ere is n<>equivalent,
procedurefor the polarizing microscope.
ZAZL J Jt u i~ () J< ' PH'Z g
E V J J>E N O Z ( > N 8 P a ( 7 (", ri7J(J J J A 'ND
discussingwas not put forward much sooner, and. in the second. place,
that even theseparate points which had formerly been accepted, and
which are now confirmed, were generally rejected or disregarded from
the end of the second war, or in some cases earlier, until a year or two
;>,go. Many of the old observations are also of considerable interest in
themselves, and have nof been repeated in recent years.
II. 1. Conatancy ofA band width
It seems to have been genera,lly agreed throughout the second half of
last century that the width of the I band varied more than that
of the A when fibres or fibrils in different degrees of stretch or con-
traction were compared. Some of the sources of this opinion are the
1'ollowing:
(I) Dozlz ( 1849) reported that t h e b and w i t h l o wer r efractive
index (I) was extremely narrow in fibrils which were slightly shortened,
a nd could sometimes be lengthened by stretching the fibril i f t h e
preparation was very fresh.
(2) KEAJJsz (1869, p. 172) observed that the width of the A band of
vertebrate muscle fibres, which he gave correctly as 1 5 p (p. 12), did
»ot decrease during contraction.
(3) KNGzr,MANN (1880) measured the w i dt h o f t h e b i r efringent
bancls (A) of fibres of fixed insect muscle. In " contraction waves" he
found that A changes less than I on shortening; there was very little
change in A during shortening to 60 per cent of the initial length;
beyond that, A and I both shortened but I continued to form a reducing
proportion of the muscle lengthi.
(4) Kor.LJKEE (1888, p. 706) states that 4 enlarges at the expense
<>f I during contracf ion, until neighbouring A b a nds come into contact
with the intervening Z.
(5) HETznrs (1890, p. 72) observed, in fixed and stained preparations
of muscle from beetles, that contraction (shortening) is associated with
11>st,;>, iiarrowing, an d t h e>i coiiiplete d i sappearance, of. the I b an d
(defined as the weakly stained region} before contraction bands appear.
(6) 14oJ,LETT (1891) states that t h e l o w r e f ractive index band
l>(*,n»»cs ><;lativcly l o>igor 1» 1»is><iv(; stretch (p. 6>1) and shorter on
(:<J>itp,>ction (p. 6!1).
( 7) HEJDENHAJN (1911, p . 6 2 3) states that the I b a n d i s m o r e
e xtensible than A .
T lic, tesfiinony on t l >is poiiit, is thus reniarkably u n i f o rm . With the
exception of KEAUsz, however,none of these authors laid particular
st> css on this phenonienon; more emphasis was generally placed on the
changes which occur in more extreme degrees of contraction (formation
of contraction bands, etc.). KEAUsz, however, on the basis of the
apparent constancy ofthe width of the A band, put forward the theory
<> 6I
 1<f 77
8 c I, E s T R U c T 7T R E h N 7) T H E o R 7 7!s 0 I' (" o N T B h (" T 7 oN
t hat th e h ig h r e f r active i n dex an d t h e b i r e f ringence of t h e A b a n d
were due t o t h e p r esence there of s u b m i croscopic rods i n a p a r a l l el
arrangement. T h e l ength of t h ese rods was supposed to stay constant
(1 5 p) as the muscle shortened, their lateral separation increasing so as
to keep the volume of the whole fibril constant . K R A Usz believed that
the I bands were liquid during life, so that this fluid. was supposed to
e nter the spaces between the A r o d l ets as they m oved away f rom on e
another during contracti<ni. Hc did not specify the forces that produced
these movements, but suggested that the rods of each A band att r acted
those ofthe neighbouring A' s.
I n recent y ears, however, it h a s b een. generally believed t ha t c o n -
traction takes place inthe A band (e.g. FULToN, 1055, p. 120). How
then has a universal and, itnow appears, well-founded opinion been
reversed, in spite of having been embodied in a theory of contraction by
one of the most distinguished of the nineteenth-century m i croscopists 1
T he most i m p o r t ant f a c t ors in t h i s ch ange seem to h av e been t w o
t heoretical point s r a ised by E N GELMANN. I n t h e fi r s t p l a ce, he d i s-
missed KRAUSE's t heory on t h e g r o u nd t h a t m u s c les can shorten f a r
beyond the pointat which the A bands of adjacent sarcomeres would
come int o c o n t ac t i f t h e y s t a y e d o f c o n s t ali t w i d t h (E N O ELMANN,
1873b, p. 161). 'J'his is admitt edly (L dilliculty, t h(>ugli it shoul<l have
been clear, independently of any theory, that thc shortening process
c hanges in some way a t t i l e s t age where contraction b ands begin t o
fol'l», T i l e s ( c(>rl(I 411C<>retie(Ll 1>o»rt I s 41>ILt J>JN( ElzMANN cl l u i l cl<Ltcd
the principle that al l f o r med contractile elements are birefringent (see
for example ENGELMANN (1006), which is largely a review of his own
w ork on m u s cle). F r o m t h i s g erielalizatiori, w h ich i s p r o b ably v a l i d
as it st Ln<ls, on(1 is clearly of great sigriilicancc, 1)c c<>ricluded t1);it t1ie
birefringent parts of a stri ated fibre must be the contractile parts, and
hence that they must bc the parts which shorten during contraction.
He thus seems to have persuaded himself of the reverse of what he had
fo»)i<i by <lire<!4»l<>ILs(»<',r»<:I>4; »I 1»s >Lr'ti<:I<:ol 10(>(i 1><', I'<;I<:Is <>»ly»I
the most c ursory w a y t o l i i s p a per o f 1 8 80 . J t i s w o r t l i i i o t in g t w <>
f<IL4(rr'cs of 41>is angl>»i(,ril,: l i rs4, 11>ILt Lri <>x1><;Ii»I<>»t;Ll <>l>s<;I'v;Lti<>»
1>ILS 1><icn OV<>l'ril>l'OW» <>» 41><><>l'<>4l<l>l I gl'<>»»<1S> >L»<l See»»<1, 411>L4 tile
ILI'gUII>(>fit »lv<>l v<'s tll<' 4>L»ll >L s»»>1>4><>I>41>IL4»I»s<>l(> c<>»4<L>lrs «L sl»glc
(lo»tl'Iri<ltll() sr(i>s1>Ln(>(> wl»(>ll sir<>I'1(>ns (IIII'Ing co» t l ' ILetlori. 1> (>tll» 1
these points will t u rl i »1> Ig;Lin iri a <lifl'cre»t con»ection (p. 271).
14 is those upi»i(>lie <>f Er«>EI.MANN 's t liat sce»i 4<> JIILvc boon ge»er;L11y
a ccepted, but it i s d ifficult t o say how far t his was due to his authorit y
an(l how .I'ILr 4<> 41(c well-l<»<>Nil 1>ll1>(ll' 1lllLlw(Ls pllblisllcd l>y J10IL I' ill,IL
in 1000. H e o b 4 ained cine-ph<>tographs of spontaneous contractions
in i»sect muscle libr<>s, ni<>stly with p o l(Lrixcd light, and c l aimed t h a t,
his results both confirmed ENGEI,MANN's claim that the shortening
268
E A R L I E R E V I 7) E N C E ON i V I D T ' I I O lr T H E A R AN D
occurs in the A band, arid contradicted the generally accepted view
t hat a " r eversal of striations" (development of dense bands in t h e
regions where I's had been in the resting Gbre) takes place when muscles
shorten greatly. But th e difference between his and. his predecessors'
results seems in fact to lie in the condition of his fibres in the resting
state. HisI bands appear to have been about $ the width of his A
bands, while the usual figures given for t his r atio are $ or m o r e.
The only explanation that suggests itself for this difference is that his
f iibres, even in th e resting state, were already shortened almost to t h e
point where contraction bands are formed, and further shortening
m ust necessarily involve the A h and. S i milarly, lm did not find a
r eversal because in t h ese fibres at r est t h e S l i n e ( w i t h t h e a c c om -
panyingN bands, which are composed of interstitial granules) appeared
as the densest part of the sarcomere, this being no doubt connected
with thenarrowness ofI. He observed the formation of dense contrac-
tion bands at the level of Z (i n agreement with all other observers)
but did not regard this as constituting a reversal because they were at
t he same position as the densest part of t h e resting pattern. H i s
di6'erences from former observations are therefore more apparent
than real, and depend on some imperfectly explained di6'erence in the
initial s t at e o f t h e f i b r es ; n e v e r t h eless, hi s c o n clusions h av e b e en
widely quoted not only as supporting ENozI.MANN's contention that
shortening takes place only inthe A bands (e.g. MEIERHoz, 1930,
p. 205)but as disproving the reality of the reversal phenomenon and
thence of theformation of contraction bands.
The other well-known work w h ich appears to support E N o z I,MANN's
view is t ha t o f SU c H THAL, KNAPPEIs and LI N D HARD ( 1936). T h e y
photographed isolatedfibres from the frog in ordinary light, and found
that theirdark bands changed. in width more than their light bands,
during bothpassive stretch and isotonic contraction. As was mentioned
011pp. 261 and 265, this is an extremely di%cult specimen from the
<>1>4ic(L1 1><>int of view, and I ca n only conclude, from th e disagreement
with our i n t e i i'erence microscope results (A. I<. Hv x L E)t and NI E DER-
(Ii:ILI<E, 1054 ) that they were not justified in assuming that their dark
l >a»d corr<srporidcd accurately i n w i d t h t o t h e a c t u a l h i g h r e f r a ct i v e
i»dcx barrds of tlic fibrcs. T h i s work w(Ls, however, generally accepted
as further evidence in support of the view that it is the A band which is
contractile. The observations of HozvATH (1052), which appear to
sliow that, the A and I bands of a glycerol-extracted Gbre maintain a
constant ratio during contraction, are subject to the same criticisms.
With thc s,dventof the electron microscope, these confusions ought
to have been cleared up at once, but they were not. HALL, JAKUs and
ScHMITT (1046, p. 38), in their well-known paper, do indeed. state that
the A band hardlychanged in width on passive stretch, but they also
269
 M 'IJSOLE S ' I ' R U G ' r l I H TC A N T I 'I'TTI<'<'IITTT<lS <) Ii' C<TNT l i A < I 'I'TON
state tfiat t f iis conlirnis .jh<oll'I'IIAI, <'I,<Tl,.'s I '<:a<<It~, whijc iii t 'lict it i s i i i
d irect contradiction w i t h t h e r m U n l i k e t h e u t lier features of their
p hotographs, t hi s p a r t i c ular r e sult d i d n o t a t t r a c t m u c h a t t e n t i o n :
even the authors themselves do not mention it i n a subsequent review
article (SoaMTTTet at,, 1947). DR A PERand H o i TGII (1949) publishe<l
very good micrographs of separated fibrilsfrom fixed toad muscie:
measurement of t h eir pl ates shows that th e A b a rul was very constant,
at about 1 5 p wi dt h in all fibr ils that were not so much shortened as to
produce contraction bands, but the authors do not comment on this.
HOFFMANN-BERLING and KA U scaE ( 1 950), using siinilar pre parations
from f r o g m u s cle, di d c l e arly s t at e t h a t o n l y t h e I ban d e x t e i u l e d
noticeably on stretching, though all their absolute dimensions are much
too sinall ( le — 2times), suggesting that eithei their pr ep<<i ations 1M<1
shrunk or the magnification was iiot correctly <letel rnine<E. ESLURM all<i
STTARAMAYYA (1951) also found the width of t h e A b and i n f i brils
from rat diaphragm to be unchanged on stretch and during isometri<;
c ontraction, b u t t o s h o r t e n s o m e what d u r i n g i s o t o ni c c o n t r a cti on .
T hese tw o p a p er s d o n o t a p p ear t o h a v e r e ceived t h e n o t i c e t l i c y
deserved. The figures given by PHrLroTT and SzENT-GYoRGYr (1953)
for the ratios of widths of the various bands in thin sections do show
greater. changes in f tl i a n in A , b u t 3 < l o ca not, seclii t<>
stay constant,.
These results are again u n s at isfactory, bcc<Luse t( lc authors assulne<l
without a check that the absolute sarcomere lengtli in each photograph
was given by the degree of stretch applied to the muscle bef'ore fixation.
Et is thus u n f o r t u n ately t h e case that t h ere is at p r esent no r e i,lly
s atisfactory electron-microscope evidence on the quostion whether t h c
A band wi dt h r e m ains constant,; on t h e w h o le, t his idea is supported
by the electron-microscope work, and is certainly not excluded. by it;.
DEMPsEY et a l. (1946), in their histochemical study of muscle, also
found. thatthe I band. became narrower in moderate contraction, until
it almost disappeared.
II. . /i <NZ«l'<Z<<ll <i<I /0'Ill I/0Ã<,l<,
" Myosin" w a s fi r s t e x t r a c ted f r o m m u s cl e b y K i i a N I : ( 1 8 64), w l i o
n amed it an d c h a r acterized it b y i t s s o l u bilit y p r o p erties an<i by t i l e
gl'<iat <><M<0 wltll w l l l c I I It IH <l<lllal <II'«' l. I< lN<I KINSMAN(NI87;ll), p. I 74)
mentions in passing that he believes myosin to be the anisotropic
substiuicc, "oli lic«; ill<it <If' lts I<<st<><:Lie<Ill<:;<II'<;a<:ti<IIIs.' T. i f . I f i<xi,l;v
(1880), in a gciicral descliptioii of' iliusculai t i ssue, w»s able t<> write:
" En fibres which )lave been acted u pon b y s o l u t ion u f s a lt , o r d i l u t e
acids, the inter-septal zones tA bands] have lost their polarizing property.
As we know that tlie reagents in question dissolve the peculiar con-
stituent of m us<:lc, my<i~<'n, it is to b c c o n cluded th at t h e i n t e r -septal
s ubstance is chiefly composed of myosin. " ( T h e " s e pta" o n w i i i c h l i i s
'70
EAST, I E H EVI D 'll N <'. I<i GN wr D ' rlT o Y T TIE A S AN D
nonienclature of the striations is based arc the 8 membranes; the
"inter-septal zones" correspond. to the A bands, and. are contrasted
with the non-birefringent "septal zones" which correspond, to the I
band.s.) Similar observations were made by SoarprLGEEand DANrLEw-
RKY (1881), who showed also that the high refractive index of the A
l>ands disappeared when the myosin was extracted. They alsofound
that adrop of myosin solution became birefringent on drying.
This viewseems to have been generally adopted (e.g. the review by
B IEDERMANN, 1927, p. 4 2 7), bu t t h e r e seems to h a v e b een n o f r e sh
evidence until 1930 when voN MURALT and EnsAr,L showed that myosin
solutions gave fiow birefringence, and that the particles were of a length
roughly equal to the width of an A band. (ErisALL, i942 ). Finally, in
I <I84 WERER made oriented threads of myo sin, and NG LL and WE EER
showed that their birefringence would account for both the intrinsic
:Ind form components of t hat of m u scle.
The interpretation of t hese results was of course complicated. by
1 lle discovery i n S ZENT-GYoRGYI s laboiatol'y (STRAUR, 1943) of t h e
composite nature ofthe material that had. formerly been known as
myosin, butthere does not seem to be any justifi cation for the way in
which the evidence for localization of at least one component came to
bc disregarded.. The chief reason seems to have been that the interac-
tions between actomyosin and AT P p r o vided plausible theories of
contraction which required,both the actin and the myosin to be
uniformly distributed along the whole of the fibrils, so that, on activa-
tion, they could form actomyosin filaments which were supposed, to
shorten by folding under the infiuence of ATP. The only evidence
adduced in favour of t hi s uniform distribution was that th e early
electron micrographs, especially those of HAr,r et uL {1946), appeared
t'o show continuous filaments running through both A and I ba n d s.
E <ozsA, SzENT-GYoRGYr and W Y o a o EII ( 1950) di d s u g gest t h a t t h e
filaments might be actin and that the extra material which causes the
electron-scattering power of the A band might be myosin, but SzENT-
G Ytin<I vi. ( I!I5 '1, p. x) later gave uli t his view.
The position appears to be closely parallel to that which led, after
1910 or so, to the assumption that shortening takes place in the A band
(sec p. 268). The experimental evidence, which on its own account
requires at least one component of actomyosin to be localized in the A
bands, was discarded on theoretical grounds, and the argument again
Involved the tacit assumption that there is a single contractile substance
{ actomyosin) which i tself shortens during contraction. A f u r t h e r
parallel is that i n b ot h cases the theoretical view received support
from some technically very impressive observations (in the first case,
HURTTTLE's cine-photomicrographs; in the second, the early electron-
microscope observations) which, however, would probably not h av e
271
 M IISODl<> 8'I'R IJ(rr «R Z A N 1) ' I'll >'lo II I I''rH () Y (! «N' i' Ilh (H ei() X
been adeq«ate t« o v e r t h row t I>c «Ider cvi<lci>cc without t lie theoi<cticaI
backing.
II. 3. '.I'he i<leo of sh(l)'n!l niole<"nles
The ide<l tha t p a s sive s t r etc h o f < l Ht r hlted r « «sclc t a kes p l »cc I)y
l ong molecules sliding past one another, r at her t h a n b y « n f o l d ing o >
stretching of chains, was put forward at l east twice before the evidenc(
disc>)ssed on pI). 20')--26)4 ha(1 1)ccn «I )l<li>>c(l. I" I H(',I>z>l( I <047, I). 7s7)
made this suggestion on the ground that the birefringence of striated
m uscle changes very l i t t l e o n s t r e t ch , ( >nd 16oRA>,zs (1948) did so i n
o rder t o e x p l ai n t h e g r ea t e x t e n sibilit y o f r e s t i n g m u s cle an d t h e
absence of change in th e w i d e-angle X-ray pat te> n; »II these appea> t«
be import ant p i e ces of e v i d ence. N e i t he r o f t h e se a u t h ors assume(I
t hat active shortening took pl ace by sliding . M O RAr.zs di d p o in t o u t
that th e d ecrease of a c t iv e t e nsion w i t h s t r e tch m i ght b e a c counte(1
for by t h e d e crease of t h e z one of o v erlap, bu t h i s a r g u ment d i f f erH
from t h a t o f A . F . H v x i . z v a n d N I z u z z o z Riez ( 1 954) i n t h a t h e
postulated only t h a t t h e s t r e n gt h o f c o n n ection w o uld d e crease, not
the number of sites where tension is generated. Bozx,zR (1936) suggeste(l
that the behaviour. of smooth muscle could best bc explained hy
assuming t ha t c o n t r a ct I«n i n v o l ved c l «>ages in t h c r e l » t iv e p<» iti<»)
of the molecules, and not in their shape.
II1. "A(",IuvATi «N" AN D r ii z 7r M vM R R A NI,
III . 1 . 1 ' k e link l)et)aee)) excitation an(l contraction,
A great deal i s k n o w n a b ou t t h e e l ectrical events w h ich a cco>npanv
excitation o f a m u s cle fi b re, an d a b ou t t h e c o n t r a ction p r ocess, b«t
very little about the steps that link them together. The interior of »,
resting muscle fibre is electrically negative to the surrounding fluid
by 60 — 1 00 )nV, the l H ) tcntial d ! A 'cicncc e xi sting a c>'«sH a very t h i »
s>irf»c() n>e>«bra)>c. When thc li bre is excited 4hr«i)gh its 1>ci'vc H«I)I)ly,
this potential d i f f erence undorgocs a t r a n sient r eduction o r r e v ersal.
'Jii the Inost fa>niliar ki i><IH ol' I»«scI() fibre (those which »r c c»I>able «I'
ILII )l I I - « I ' - ))«I)c 4W ) l < 'I) I )) I ' ( ) HI )«IIH() I < ) <III'c(!li <)IO()4>'Ic)ll Htl>)>«I<lt><)I)),
t his decrease ol' i n e in braiie p « 4enti»I ( ' "depolariz»tion" ) p r o p a g l t c s
itsol('along tho wh«I() Ic>igth «I' thc fib> c hy <1 process which is essenti»lly
the same as the cond«ction of an imp ulse along a non-myelinated nerve
fibre. I n o t h e r c a ses (the slow f i b res of f r o gs, and «>any a r t h r opod
muscles) the depolarization spreads passively for only a short distance
from each neuroinuscular junction, but the whole of the length of e»ch
muscle fibre i s n e v ertheless brought i n t o a c t i o n b e cause it r e c eives
numerous nerve terininations distributed along its length. I n a l l cases,
h owever, the electrical change is a r eduction (or r eversal) of t h e
') 72
A <!q~iyA~ri <) N A N 1) 'I I I I ) 8 M >l M R R AN > l
p otential d i f f erence across t,he surface meinbrane. I t i s a l s o f o u n d
that, if this potential difference is reduced by any other treatment of
the fibre (passage of cu i mnt ; K C I s o l u t i o ns ; a p p l i c ation o f a c et y l -
choline to an endplate), the part of t h e fibre which is depolarized
contracts (K() >)zi.z>i, 194f) ). This suggests strongly that the membrane
potential change is the essential thing for setting off the contractile
process, but if so there is the difficulty of explaining how this electrical
cha)>gc, which c»n exert » direct influence only on the membrane itself,
i s able t o c a use fibrils i n t h e i n t e r ior o f t h e f i b r e t o c o n t r a ct . T h e
distances involved are considerable: t h e fi bres of skeletal muscle of the
frog are commonly over 100l< in diameter, while jn Crustacea the
fibres reach 0 5 mm or m o ro , I <'urther, A . V . H r r,L has shown (1949c)
that the link cannot be a substance which is released at the surface
membrane and reaches the fibrils by a simple diffusion process, since
this would.be too slow to account for the very rapid onset of heat
production and of the contraction itself.
A suggestion which has occurred to many people isthat it is not
the membrane potential chango, but the currents in the interior of the
fibre,that are the immediate cause of "s,ctivation" of the oontractile
s ubstance. I f t h i s w ere the case, there would be n o d ifficulty i n
explaining the speed of the onset ofcontraction. But KUzzrzR (1946)
pointed outthat contraction isproduced even by a uniform depolariza-
tion of the fibre surface (e.g. by immersion in a solution with raised
potassium concentration)when there should be no current flow; and
'srzN-IRNUDszN (1954) has shown that when a muscle is caused. to
contract by applied current in conditions where an action potential
is notproduced, the contraction is confined to the neighbourhood. of the
cathode, where the membrane potentialis reduced, while the region
midway between the electrodes, where the current density inside the
fibres is a maximum, is passively stretched.
It is thus highly probable that the membrane potential change itself
is the essential factor for causing activation of the contractile material,
<l>«l we are left with the problem of the nature of the link between
men>br»nc and fibrils.
lll. '). 'IV)e 7~tine
The g lineis a narrow band of high refractive index at the middle of
the I band. It is widely, though not universally, believed to represent .
a more or less continuous membrane which runs across the whole fibre,
uniting the fibrilsto one another and. to the sarcolemma. Many
authors hs,veascribed to ita purely mechanical function, keeping the
Htriations of the separate fibrils in register and perhaps transmitting
tension insome way to the sarcolemma; the dHBcuhies in this idea
have been wellstated by BzNNzTT (1955). But itsapparent continuity
278
 MUs o L E s T I L l r <' T l r >L>: AN » ' I ' lI I! r) lr ) >:s 0 I.' 0 0 N T >LA (>T )0N
and at t a chment t o t h e s a r colemma a lso sugge ted t o T i L)os (1924;
MAT THAzz and Tir o s , 1955 ) that its function might be connected with
the activation o f t h e c o n t r a ctile f i b r i ls . I n T r z o s ' s v i ew , t h e a c t i on
potential itself travels along the Z membrane, which he believes to be
invariably a spiral stru ct u re ; i t s e ems clear f ro m e l ectrophysiological
work that t h i s cannot be th e case, at any r at e i n n o r mal cont r actions
o f vertebrate m u s cle, w h er e t h e a c t i o n p o t e n t ia l i s c l e arl y a s e l f -
p ropagating c h a nge i n t h e p o t e n t i a l d i f f erence a c ross t h e s u r f a ce
membrane. However, the possibility remains that the 8 m e mbrane
is concerned with conveying to th e m y o fibr ils the influence of a reduc-
tion of the potential difference across the surface memk)rane. BF NN v'rT
(1955, p. 54), on the basis of electron micros«oi)e observations, has
recently pu t f o r w ar d t h e t h e or y t h a t a n e x c i t a t or y i n fl u ence is «o»-
ducted inwards from the sarcolemma by the sarcoplasmic reticulum an<i
conveyed to the myofibrils at the S lines (see also p, 276 below).
D r. R. E . T A v L oiL and I r e cently d evised an experiment t o t est t h e
hypothesis that the 8 m e m b r ane is specifically concerned in the inwar<l
spread of activation (A. F. HUxLz Y and TA YLo>r,, 1955a,b ). If this is the
case, then presuinably it is the potential change at the attachnients
of S m e m b r anes to t h e s arcolemma t ha t c o u n ts, and n o c o n t r a ction
wouk<I be c x p c ctc(l t o f < )ll<)w a k)otonti;LI cl>a»gc wl>i«i> i»volvo<I;>.
s mall area of m e m b r ane l y in g e n t i r ely b e t w een t w o a d j a cent Z l i n e
atta«hruorrts. Wo achiovod this situatio» by bri»ging a ])ipette with
a squared-o6' tik), diameter ab out 2 fj , i n t o c o » t act w i t i > th e surface
of an isolated m uscle fibre t ha t c o ul d b c o bserved and p h o t ographed
through a polarizing microscope. The potential difference across the
small area of membrane opposite the tip of the pipette could now bc
r educed by m a k i n g t h e i n t e r io r o f t h e p i p e t t e e l ectrically n e gati v e
relative to the bathing fluid. The resistances at the tip of the pipette,
both that of the "seal" of the tip to the fibre and that of the slnall area
of meinbrane itself, are high enough for the current entering or leaving
thc l)ipctto t() k)c to() 81»rrll to pro<i»co appr cciabl«<;I>;L»gcs in peter>t i;LI.
eitl>or inside the fibre or in t h e b a t h ing fl ui d o u t side the pipette ; t i >is
is true even if the membrane opposite the tip were to undergo an IL«t io»
l>et<>» t i>LI.
Tl><) r»»sci« flb>'«w<LN sligl>tly >It>'«l«l>«: I, s<) tl>;LI th« Z l i » <:s w('>'«
about 3 p apart ; t h e 2 f L pipette could therefore be placed either
opposite a 8 line (centre of an I b and) or in the space between two
adja«(>r>t R'I> (ol )1)»sit« all 3 barul ). Ir> thc for'rl>cr' case, wo four><i tl>;Lt (L
moderate depolarization ( 20 — 40 mV) caused a l o c alized cont r actiori,
but in the latter case, a potential several tiinos hL>gcr could be applied
with no result a t a l l . I <'urther, when shortening occurred, it w a s con-
flr>«<I t() tho f k )<L>>(lok)k)ositc the pipctt c, ar>d spread o» ly a r>u)dcr;Ltc
distance inwards from the surface of the Gbre. A contraction of this
274
A O'I'T.VA T T0 N A N I) 'I' I f l " . Z I>ti.l:MB S A N I :
kind is shown in Fig. 4; the pipette in this case was 4 p in diameter„
which isabout the largest that can be used.without overlapping more
than one Z line, though it is too large for the space between two adjacent
Z's. The contraction spreads further inwards than was the case with the
2fi pipotte, but i s ot herwise just the same. T hi s photograph also
illustrates in passing the fact that the shortening takes place exclusively
i» the I ba nd, the two dark .4 bands being drawn together without
changing in width.
These results are entirely consistent with the hypothesis that we
started from, namely that the influence of membrane depolarization
which activates the contractile substance is conveyed along 8 mem-
i )ra»es. T h e e x p e r i m en t a l s o s h ow s t h a t t l > e r e sultin g a c t i v a t i o n
afl'ects only the half-sarcomere on either side of the S membrane in
question; in I<'ig. 4 the contraction spreads about 10fr inwards but
does not affectthe adjacent I bands which are only about 2 p,aw ay.
It is not actually proved that t,he visible S membrane is the structure
concerned; it may be that the activation is conveyed along some other
structure nearthe middle of each I band.. The anatomical evidence
reviewed inthe next section does however show that the S membrane
has the required characteristics, and it seems most probable that it is
thc structure «once>»e(1.
III. 3. Continuity of the S membrane
The 8 line, which is seen as a narrow band of high refractive index in a
fresh muscle fibre, is also very conspicuous in isolated fibrils, whether
examined by phase microscopy or in the electron microscope. It
usually appears as the densest part of the fibril, as i'egardsrefractive
index in the light mi croscope, electron scattering in unstained and
unshadowed electron-microscope preparations, a nd t h i ckness i n
shadowed fibrils under the electron microscope. There is a good deal
of evidence that these dense lines in the separate fibrils are connected.
t ,o ono another across ti l e » >us«le fibre. T h i s e v i d ence falls i nt o t w o
groups; the first is froni observations on fresh muscle while the second
is from examination offixed and stained preparations.
' I<)vc>ILk very co n v i n c in g p i c cos o f e v i d ence i n t h e f i r s t o f t h e s e
ciasscs date froui th e last, contury . J k>LAUs> L (1869, p. 11), SOHua.o>rrr
aud. DANU,zwsKv (1881) and K o LLxKER (1888) all observed that
. ntinuous structures remained at the position of the S lines when the
r«st, of the fibrils was renioved by dilute acid; t h i s i s particular1 y
n otable in t h e c ase of K o L L i KmiL's observations since he w a s u s i n g
insect fibrillar muscle, in which the fibrils, or sarcostyles, are separated
k)y large amounts of sarcoplasm rich in granules.
In the second class are the observations of E mi)LaLzDT (1899) and
HEIDENHAIN (1911, p. 613), who were able to stain structures uniting
27>)
 Nu s o i >: 8' I ' i i l ! (! 'i'i! ><I> A N » ' I' » >i<> fi iI!s « Ii ( ' ( > N'i'l(A (!r ( ( > N
the Z lines of adjsccnt Jibriis cvo>i whc><o tlioy wc><o separate<i i>y;>, bi <>ad
b and of sarcoplasm, and also r u n i i in g f r on i t h e sarcolemma to t h e Z
of the most superficial fibrils. T h i s was confirmed by voN Boo r ( 1 937),
who pointed outthat the 6ne membranes uniting the Z's of adjacent
f ibrils stain d iJFerently f r o m t h e Z ' s i n t h e fi b r i l s t h emselves. T i z o s
( 1955) has also demonstrated the contin u it y o f Z i n b o t h f i b r i l lar an d
non-fibrillar m uscles of insects.
A somewhat similar conclusion is reached by JJKNNFTT slid PoRT>>H
(1953) and Bz ii(N'ii',TT (1955) from very beautiful t hi n sections of inuscle
under the electron microscope. They show connections between the
Z's of adjacent fi br ils and between the sarcolemma and the Z li n e s of
n earby fi b r i ls, bu t t h ese connections are very m u c h t h i n ner t h a n t h e
Z lines w i t hi n t h e f i b r i ls , an d a r e e a sily d i s t o rted i f t h e f i b r i l s a r e
displaced longitudinally i n p r eparing the specimens. T hey r egard
these connections as part o f a " s a r coplasmic reticulum " w h i c h e x i sts
in the spaces between the fi b r i ls, and c onnects wit h t h e s arcosonies:
t his reticulum w a s w el l d escribed b y K o r L .iKzn ( 1 888) and B m " z i p s
(1890) in 6bres stained by procedures in which the 6brils were dissolved
out or were swollen until they did not interfere with the image of the
sarcoplasmic structures.
I t seems legitim ate t o c o n clude t ha t t h er e ex ists in t h e m i d d l o of
each I ba nd a s t r u c t u re wh i ch is connected to t he sarcolemnm,, wliich
runs right a cross tlic l i b re, a>id of w l i ich t h o corresponding Z l i n es of
the indivi dual fi b r il a for m a p a r t . T h i s w h ol o st r ucture niay p o r l iaps
be called KnwUs>,"s membrane, or Z m em brane, in contradistinction to
the Z lines in an individual fibril (voN Boo>i., 1937).
T he existence of a " c o n t i n u ous" st r u ct ure in t hi s sense must not b e
takon to moan that t i>ore is a cuir> ploto >nemb»' nc, like a, cell ino>nbra»o,
crossing the fibre in each I ba n d. T h o o lectrical ovidonce clearly sliows
that such a thing does not exist, the fi br i nterior liaving a fairly low
resistance to longitud i nal ci irrent ( K > T z, 1948). If t h e Z m e m b r a ne is
«I' ll>o ><>w»o» >it»r(»>s a <><:ll »ic»>l>raii», l»;vi»g a l »w l >o>»>(»il>ility l'<»
ions and a high electrical resista>ice, it must havo extensive porforati»ns
th>ough whi(l i i on s can n i » vo ; i l ' i t i s c o n t i n u »us iu t h o sense <>l' iu>t
)ascii>g porf'«rale<i, il, »»»<t <>ll'<!> «»Iy;>, v<»y Nligl>t r<wist»,»«:; l» t l><;
ni«vol»o>lt, <>l' i«>iH.
'.lux>iis»i of <!oi><lu<;li<»> «Los><g Z»ieir>6>'u>i«s
Ill . 4. il l «',
ll w o a l l o w « l » '>>(:ives L» c(»>cIU(J« l >.'»»1 t l»s cvl(loiico tl i ilt c> lcli Z
membrane isconcerned with conveying an infiuence of surface depolari-
zali<>ii l<> aclivi>lo tl><> I>;>1l'-sacro»>(!>'(s wl>i(;t> lio oii c i t l>or si<l(> <>I' it,
the quostion at o nco arises, what i s t h e n a t ur e of t h i s i n t luencc, and
how is it conducted. Th e only cluo to this that the oxporiments provide
is the fact that the contraction does not propagate itself inwards, but
270
A (i'i'> v A'ri (> N A N i > ' i 'n IC z >>> ICh>81(ANY'
spreads for a (listance which increases with the voltage applied. and with
the size of the pipette. The experiment does not prove conclusively
that aself-maintaining inward propagation does not occur in a perfeotly
undamaged fibre,since the fibres had ceased to give ordinary all-or-
nothing twitches by the time we managed to observe these local effects,
and it is conceivable that there is normally a propagating meohanism
which had bythen been lost. But 6bres in thisstate can give apparently
normal twitches when the membrane is depolarized. by applied. current
( Bi>owN and SicHEL, 1936; confirmed in unpublished work by D r .
R. Z. TxvLoa and myself).There is therefore no need to postulate a
self-propagating mechanism, and in any case our experiments show
t liat a graded activation can spread, quite a long way m. This seems to
excluele such mechanisms as crystallization (HiLL, 1949o) and "activated
di8'usion" (diffusion of a substance whose presence causes more of the
same substance to be liberated) which have been suggested as mech-
anisms for the rapid activation of the fibre interior in response to
surface-membrane potential changes, since they would. be expected to
be self-propagating. At t h e same time, the fact that the contraction
did notreach nearly to the centre of the 6bre would be expected.on any
mechanism that was not regenerative, since the pipette covered only
a very small sector of the edge of the Z membrane, and the udiuence
of depolarization on thissmall region was spread out over a broad.
front as it was conducted inward.
There is nothing at present to contradict the very tentative sugges-
tion that the mechanism may be an electrical one. If the Z membrane
contained.channels whose lumen was connected to the external fi uid,
and whose walls had a high resistance, then the potential difference
across the walls would follow that across the surface membrane of the
fibrewith a lag depending on the size of the channels, the capacity of
their walls, etc. Bough calculations show that the lag would be very
small even if the channels were as sinall as 100 A diameter, and were
i»sulatod from tho sarcoplasin by walls with a capacity of 1 pP /om~
such asis found in the inembranes of many cells.
IJI. 5 . l, » wgiLN<li»aL 8prea<J,f acti(>ation
o
'I'1>e><> is also tlio question l i ow a c h a ngo spa+d i ng i n w 'ards along th e
Z membrane brings about the contractile process which presumably
occurs in the nearest half-A-band on either side. The striking feature
; il>»ut thi s f inal s t age of t h e s p r ead o f a c t i v a t ion i s t h a t i t g o e s n o
further than this: no shortening was seen in the I bands on either side
<>l' tho one to which the pipette was applied. If diffusion of a substance
from Z is responsible, then there must be something that limits the
range ofdiffusion, e.g. the dMusing material might be used up in the
6rst halfof the adjacent A bands, or there might be an impermeable
277
 MIISC I> l~l i8'I'I< ll<«I'll I< I'l A 8 » ' I ' l l I~l<I I<I<s
I <I I' <' <IN 'I'I<A < "I'I <IN
layer at the position of i ll . T h e l i m i t a t ion of t h c spread of acti v at i on
would however be directly explained if the change was some alteration
in the actin filaments, which was conveyed along them from the Z
l ine, since they t e r m i n ate at o r b e f ore th e m i d dle of t h e a d j acent .0
bands. O t h e r p o i nt s w h i c h s uggest t h < t n c t i v a t i ol i m a y b e a c e»I»-
p anied by a c h a nge in t h e a c ti n f i l a m ents are mentioned on pp . 3 0 f
and 305.
Il I. <f. 'I'he fI<II<'tioII«l I<ilit i I I, ,>(I'i«terl, nuu8<1<.
I t is customary t o t a k e as th e r epeating uni t o f t h e s t r i a t ion p a t t ern
the sarcomere, which is defined as the region bounded by two adjacent
Z lines. T h e e x p erinients described here siiggest that t h e f u n c t i onal
u nits are centred on the Z lines, and not separated by theni, so that th e
unit consists ok'a Z line wit h th e I b a n d in w h ich it l ies and the half =f
band on either side. W e n ever saw a contraction inv olving one-half. of
an I band only (though our pipettesmay not have been small enough
to achieve this if it is possible in principle, and it is also conceivable
that a contraction at one side only of the Z line might have been
mistaken for a weak contraction involving both sides). Also, as men-
tioned above, we never saw any shortening of the neighbouring I
bands such as woulcl have occurred ifcontraction hnd taken plac«, i»
both halves of' ca«ll of' the ~'I bali<la adjacent to thc point ot' stirnulatio».
There are, however, occasional records inthe literature of contractio»
waves in fixed pr eparations of insect inuscle where the degree of co»-
traction is strik i » gly di fferent in th e 1IIIlf-sarco»icres <>n cithel si<le of;I,
single Z line (HCLLETT, 180i, filg. 1<I; T r zc<n, k<)5'>, fig. 39).
III . 7 . Ot h er f'«wrtior<8f othe Z 1<'ile
It wa s m e n t i oned a b ove t h a t t h e r e ar e g r eat d i fi i cukties (BENNETI,
1955) in the idea that the Z membrane conveys the force of contraction
to the sarcolenunn,, but it reniains possible that the Z line has a mech-
a nical fun ct ion a s w e l l a s b e in g c o ncerned i n t h e a c t i v a t io n o f t i l e
f ibrils. W i l klili c a ckI » i yo fibr'ik tho r o » r u s t b «. So»ic s t r uck ural l i ri k
which keeps th e I l l y osili f i l a »ients a l ongside one an other i n e n cl> .f
b a»d, null a » e t he l l i » k w l l i « h k e eps each sct o f a c t i n fi l n m c l it s i »
I'<IglHI »I'. I II<) <)I«' ll I'<)»»l l <',I'<)gl'ILfIIIII <II I i<PI)<< ll{ I l)55) Hll<)w cl'oss-li»l s
between the filaments of the primary array (presumably myosin) in the
• 'l k)Ii»<l; Il>»Illy I)< I kl<'s<'I frllnf kcof) fli c » l y <Islll flhl»lcllts ILlig»ed, hilt I I
N<) Lll<<l'<< <lllll»<>l b<l «')I'I'<~nfI<)»<f»lg < ll'<Iss ll»ks b < tw «<;» t l I < I; I c t » I f l h l -
inents, or the sliding » l o ver»cut would be impossible: connections could
o»ly <Ixtnt at f li c kI<lsitio» <>f f1I<I 7i li»c, wflcl<c tll<ry would liot int o> f<;I< *,
with the movement of the myosin fila»1ents an<i l.lleir set of cross-li»ks.
I t is t h c rcf<>re Ii<lccss:lry to k eep i l l B i i i l d f h c p o ssibility t h a t t i l e Z
line hns also the function of keeping the actin fiila»ients in alignment.
278
l i V P O T H l ' s i n F < ) R T 11 E Ilrz <"H A N I S M O F C O N T R A C T I O N
IV. A HTPCTHzsrs FQR THE MEOHANrsM oF CCNTRAOT roN
Most, if not all, of the hypotheses that have been put forward in
recent years as explanations of muscle contraction on the molecular
level have assuined that protein chains, running longitudinally in the
muscle, shorten by some kind of f o lding or coiling. These theories
have differedin the type of folding assumed, and in the nature of the
forces that were supposed to produce the folding, but have been
remarkably uniform in assuming that shortening takes place in each
filament at a number of points in series, i.e. the decrease in length of the
whole filament is the sum of the amounts of shortening that have
occurred at the different points of folding along its length, while the
whole tension in the filament is exerted at each of these different links.
This idea appears tohave been supported especially by the changes
of structure t ha t w er e f o un d b y A s T ErrRT and D r c x r N soN (1940) to
occur when a myosinfilm is stretched or made to shorten, and by the
appearance ofcontinuous fil aments which was suggested by the early
electron-microscope studies of muscle. On the other hand it is very
difficult to reconcile with the many lines of evidence, reviewed. here
and by H+NsoN and H. E. HrrxLEF (1955), showing that the individual
filanientsdo not change in length appreciably when a muscle contracts,
anyhow over thegreater part of its normal range.
If then we are to replace the hypothesis that shortening is generated
by a fi lament folding at a number of places in succession, by the hypo-
thesis that two types of filament slide past one another, how are we to
suppose thatthis relative movement is brought about f So far,three
broad. suggestions have been made:
(1) The filaments move so as to increase the number of points at
which some chemical interaction can take place between thein (H. E.
HrrxLEv and HaNsoN, 1954).
(2) The filaments of one type are capable of small changes of length,
b ut these take place cyclically, the attachments between the t w o
filanients being broken and remade so that the overall result is relative
movement between the filaments without appreciableshortening of
e ither. T his t ype of" scheme, with the f urther suggestion that t h e
«ycki«al cf<angos might t ak e p l ace in th e actin fiilaments by successive
depolymerization and repolymerization, has been put forward by
l -lANsoN and H. E . H U x L E F (1955), and by AUrIERT (1955).
( 3) A r elative force betwceii adjacent fi l alnents of t h e t w o k i n d s i s
generated at each of a series of points within the zone in which they
overlap (A . E . H U x L E F an d N I E DERGERKE, 1954; d i s cussed also by
H~NSON and H. E . H U XLEY, 1955 ).
So far, there is nothing worthy of the name of evidence either for or
against any of these three general possibilities. The second has the
279
 > >H('ri g H t R l ' ( « t ( ' t < t r Liar>) rtr r>tr()>t>>PH (i > , ( ( ) N r a il ( r rr t ( ) t<
Adva«tage ol' bringi«g i n s o»le of t h o i n t eresting pr operties of. actin,
while the t h ir d p r o v i des an e x p l anation fo r t h e p a r a llelism b etween
the isometric tension generated in s t et anus and the width of th e over-
l ap zone, when a m u scle is extended beyond it s resting length (A . I t .
HUxLEY sn d N I E D XRGRRKR, 1954). The same Authors pointed out
that their scheme would acco>int for the known correlation between
n arrownesa of s t r i a t io n a n d s p ee d o f c o n t r a c t i on , b u t t h i s c o u l d
probably also be fitted i nt o eit her of th e ot her. schemes.
I t ia possible that h i g h -resolution electron i n i croscopy niay h elp t o
d ecide between t h ese alternatives, bu t i t m i g h t n o t : s o m e k i n d o f
s tructural lin k b e t ween the tw o seta of filaments is required on any o f
these schemes, and even if t h e l i n k s ar e seen, it n i a y n ot, be possible
to say in which way they are acting. Another way of trying to decide
between t he m i s t o f o l l o w o u t i n d e t a i l t h e r e l a t i onships b et ween
observable quantities (tension, heat production, etc.) that wouhl be
expeoted on each, and seeing whether any of the schemes can be
e xcluded through failure to fit in w it h th e experimental data. A s I
have stated t h em , t h e t h r ee t y pes of m e chanisin are riot specifie<1 iii
enough detail for making predictions which can be checked experi-
r
mentally ; l > ol'ot e Il)ia et»i bo (l<»io,;L Ho<I>tot)co of' events lii i k it>g tl>c,
Hu»l )ly <)f cl)ct»i<u>I <')»orgy to I l>o r>1(",cl>'Lt)i(uLI Hystc»i «>»Ht l>0 H»ecifio<l,
together w i t h t l >o f a ctors w l i ic h c o>ittol t h e r s t o s of ' t h o r e a ct io«H.
t)clio>>los wll>cli (L>'0 put fol')v>ll.'d iii t i lt s ltl>to>tilt of detisil At tihe pi'0801>I
time must necessarily be h i ghly speculative, but m s y n e v ertheless be
helpful both in sl iowing how fsr i t i « s y b o possible to go in explaining
the known behaviour of muscle,and also— more important — in suggest-
ing experiments which may exclude particular hypotheses or groups of
hypotheses.
One such scheme' (belonging t o t h e t h i r d o f t h e c l asses mentioned
above) waa worked out in some det>,il. by the author in the summer of
1964. It f i t t e d A, number of the known properties of muscle fair'ly well,
will»»>i r r»L>>y;>) I)il,r'»ty IHLHI»l> LI<:H,;L»<I ii I I) < :r<)I'<)roH(><)t>is w<>rt,l>
w hile t o g i v e L i i a c c ount o f i t h o r o . I t w s s f r s t nod p r i m a r il y w i t h
rofot'otic(', t() I l )<; "HIi(lir>fr" li y ls>tliosis >uul I<> tl>o rotations bc t weo«
I<»L(l, Hl»»'ire»>l>g rL»<l I><»LI »I'()(l»<)ii ><»l, I»>i Ii l ) <) ( t l »tt»>('sLI t'()sL<'Iri<)t>H
»ruvisi»t»Lily >LH>»>r»(i<l I<) (rr><lor lie I I»; Hto »H <)I' I l)o c<»)tr Lcii(»t »roccss
1)(t v() l)o()n (ll)oH(>t) H<) >Ls t 0 l>o (l()«H>Htctlt w) t I) t l)o i n s t« f c » f i l l>'OH ol
tl>0 beilsviot>F ol i >zt r,'NT-4YURGYI s gf ycc>'instie(1 )nuscle pi'epsl'at;iol>
()V>rlttlr:>Ls I <)f)fi ).
The hypothesis will first be stated in general terms, and then a
«)Atl>o«istical t) oat)no)it w il l b o g i v oii i « o r ( lc r t<) derive form ulae foi
tension And hoot p r o d u ction, ss f u n ctions of t l>c speed of shorte«ing,
f or chockii>g sgsiiist t h o r c l s t io>>ships found oxporimontally b y A . V .
HE'LL.
oSI>
i( t>'V PO'>'>1'>LSIS Y( ) )L 'I" » >i tt)io BAN ( S M A ir OO N T R A C T I O N
IV. 1. Statement o f thehyI>others
The generalidea is that each of the filaments of one type (provisionally
assumed to be the myosin filaments) has side-pieces which can slide
along the main backbone ofthe filament, the extent of the movement
being limited, by an elastic connection. T hese sliding members can
combine temporarily with sitea on adjacent actin filaments, the con-
nections being formed spontaneously but broken only by a reaction
requiring energy to be supplied from metabolic sources. The essential
feature of the system is that the rates of the reaotions by which the
Myosin
f ilurnent
Actin
filament
Equilibr ium position
efsr site ~ )
Yig. S. Diagram iilustrat ing the mechanism by which it is assumed that tension
it< generated. The part of a fibril which is shown is in the right-hand haif of an
;i band, sothat the actin filamen is attached to s S line which is out of the
picture to the right. T h e a rrows give the direction of the relative motion
between the filaments when the rnuscie shortens.
connectionsare made or broken are assumed. to depend on the position
of the sliding member relative to the backbone of ita myosin filament.
This is not difficult to i magine if we suppose that the reactions are
catalysed. by enzymes which are fixed to the myosin filament, or perhaps
actually form part of it.
The essentials of the scheme are illustrated in Fig. 5. The contractile
element shown is to be thought of as lying in the right-hand half of ari
.I band, so that the neareat 8 l i ne, to which the aotin filament is
attached, is OB' the picture to the right. D u ring shortening, therefore,
t,bo actin filament moves to the left relative to the myosin filament.
' I.'lio <listunco of A , t h o a c t iv e site on t h o a c ti n fi l a m ent , f r o m 0 , ' t h e
«quilibrium position of the sliding olement on the myosin filament, is
denoted by x (positive if A is to the right of 0). During steady shorten-
ing, x decreases at a constant rate. The rate constants for the reactions
which «lake and.undo the connection between 2 and 3f are denoted
by f and g respeotively; t h ey depend on x in t he manner shown in
I<'ig. i).
The system works as follows. I n i t ially, the groups 3I a nd A a r e
detached; 3I oscillates back and forth about its equilibrium position 0
as a result of thermal agitation. I f 2 h a ppens to be within the range
281
 M IJS(lI<I<l H'I' l t l > ( " I ' i >I(14 A(<I I> 'I' ll I((> II I (<IS (> I<' ( >(>N'I'it A ( " I > l ( >'.(
of positions where f is not zero (i.e. where the combination of 31 with A
is catalysed), there is a chance that combination will take place; when
this has happened the tension in the elastic element will be exerted.
on the actin thread. The region where this combination can occur is
to the right of 0, so that the tension in the elastic element is in the
directionto help the muscle to shorten. The A3I combination moves
towards 0 as the muscle shortens; there is all the time a chance that
w1
f ~
I
I<'ig. 0. Dependence of f and gc on a. Dashes,f, i.e. rate constant for formation
of links betu een actin and myosin by reaction (I). Continuous line, (>, i.e. rate
(onstant for breaking links by reaction (2). The unit of the ordinate scale is thc
value of (f I- >g) at, x =- h.
t he lin k w i l l b e b r o k en , s i nce g i s f i n it e e v ery where (except a t t h e
p oint 0), but th e chance is small until the group passes 0; g t h en
increases greatly and the A3 f li n k i s s oon broken, preventing the
tension in the elastic link, which is now in the reverse direction, from
holding up the shortening of the muscle. At lugh rates of shortening, a
l arge proportion of t h e l i nk s w il l n o t b e b r o ken i n t i m e t o p r e v ent a
considerable resistance from being gcncruted iri this wuy; t h e s peed o('
<Hhortclul>g of Itli ulilo<tdcd IliuHC/0rc>t('llcH I(H I Ill>lt wlicll t <hIH I'eHIHtllll('("
JIIHt c(11>u ls t1>c fol'(>(' (»'o(ill(;(',(1 l>y t f>c lil>kH to tl>(', I'ig(>t of.' 0.
We Jiavc t i t c i t l y u Hsunicd (J I(tt tJIOc(>liibuiatu>li ol A a>i d 3I
place spontaneously with the equilibrium in favour of the combined
state; h e nce i t i s n e cessary t o p o s t u l ate t h a t e n ergy i s p r o v i (le(l in
order to brcuk (Jic link . 1 (, would bcili k eeping with S zsNT-4v o l t o r l ' s
work and with r ecent work on g lycerinated fibre models ( asm,,
1965) to suppose that t his i s b rougl it u,bout b y s o i n e h i g h -energy
phosphate compound (denoted by XP ) un i t ing with a s ite near A.
After thc A and 3f gr o ups have Hepu,rated,XP is split und its fragnients
are detached, restoring the initial conditions, except that now A is iri a
>8 >
A II V r ( > I 1114SIS V O R T i l l < ' M i < CI I A N I S M O F CO N T R A CT I O N
position where f is zero and recombination is not catalysed and. there-
fore does not occur. As the muscle shortens further, the A group we
have beenconsidering moves on to a region where itmay combine with
the next 3f gr oup further to the left on the myosin chain, while the
next A group tothe right on the actin chain comes into the picture and
is able to combine with the i1I group that is under discussion.
This sequence ofevents must be supposed to take place at a number
of sites on each filament within each A band, the sites being staggered
so that they come into action asynchronously as the muscle shortens.
The overall tension in the muscle will therefore not fiuctuate appreciably
as thelinks are made and broken.
The reactions that have taken place during the cycle are:
A + 3I --~ .:>3I (rate constant: f ) • (1)
43f + XP ~ A YP + 3J ( rate constant: g) . . . .( 2 )
EXP — > A (- X + P0 4 • (3)
In the resting state, reaction (1) must be prevented from occurring,
s o as to allow th e muscle to lengthen or shorten passively. T h i s
might be achieved either by inactivating the enzyme which catalyses
reaction (1), or by stopping reaction (3), which wouM leave the A sites
blocked by theattachment of XP molecules,or by some independent
change in eitherthe A or the 3f groups which prevents them from
uniting. For the sake of defmiteness, the second of these assumptions
islnade here. A c t i v a t ion of t h e contractile substance then consists in
causing reaction (3) to take place; it will be assumed that so long as
u ctivation persists, t hi s r eaction occurs fast en ough fo r i t not to be
a limiting factor. (Some reasons for assuming provisionally that t he
activation change, whatever it is, affects the actin filaments and not
the myosin ones,are given on pp. 278, 301, and 305 ). Further, it is
assumed for the sake of simplicity that the back reactions are negligible
in all three cases.
Tlie reason why the rute constant g has to be given a finite value
('(» positive us well us negative values of x i s t h a t o t h er wise the side-
1>icc(;H thai, liappen to be attached when activation ceases (in the sense
to o k (liat no more new attachments areformed) would remain attached,
anfl the muscle would remain in a s t ate of partial rigor instead of
returning tothe resting condition. This overlap of f and g causes a
steady turnover of attached sites even when the muscle is stimulated
isometrically; t h e resulting evolution of heat corresponds to Hii,i' s
"maintenance heat."
It is provisionally assumed that the sites on each filament are far
enough apart forthe events at one site not to be affected by the
situation at nearby sites. There is no need to assume that the distance
283
 I>1 <' S(' I • 1. 'S'I' ll I I <''I' I' I< I', A )< » ' I ' » I ',( > ll I I',S <11' ( ' < ) i'«> 'I' I< A (''I' I ()N II V I'( ) T l l l«>a I S I ' ( ) u ' I ' l l I«> M «>
i «(> BAN is>>1 Or«' CON T R A C T I O N

a part of t h e l e s i t e s o n e ac h m y o s ii i f i l ame>it is t h e s a nie a s t h a t and the corresponding average force is obtained by d i v i d ing t hi s by l .
between A sites on an actin filanient. Tlie total tension in th e muscle is the sum of the tensions generated
by all the contraction sites wit hin one half-sarcomere; t h e n u m ber of
IV. -". zlIathe))>atieatJ'o)))>ulatio)(,
these sitesfor a muscle of 1 cin2 cross-sectional area is nw/2. Hence P,
Consider a large nuinbe> of contia ct,i<»i sites all wit li .1 i» t l i c s a»>c t lie tension per square centinietre, is given by :
p osition relative to 0 (1eig. 6), i.c. all h;iving the saiiie value of x . I . e t
n be the proportion of' these sites at wliicl> 1 li(,1/ is eo»>bined witl> the; -- )na/' I
P— nx dx.
corresponding A . )
We have
The >elations (4), (6) and (0) do no t d epend on t h e p a r ticular
i~)(
= (I — n)/' — »</ assun>ptions that a r e b e ing m ad e concerning th e m a n ner i n w h i c h f
<>I
Ii»(l (/ va ry w i t h x „ f, o i n t r o <li>ce. these assumptions, we m u st i n s ert
2')i I lie v;il«es of' /' and g which are indicated in k'ig. 6, i.e.
or — / — (./' I-!/)»
Ox
x < 0: J =- 0 and g = g 2 j
w here v is th e v elocity w i t h w h i c h t h e A fi l a m en t i s s l iding past t l i e 0 < x < /( : f = frx/h and g = g~x /h;
3I filament as a result of' tlie shortening of the muscle.
x> / <: f = 0 a n d ( / = g,x /h.
Now v = a V /2, wl>e>e a is tl ie sa> co»>ere lengtli a>id I'' is tlie rate of
shortening in m u scle lengths pei sec»«<1, so that Iolving equation (4) with these values, and taking V as positive (i.e.
,s I' 2)(, f l>e muscle is shortening, not being stretched) we find :
-

./'— (J' ' ,!/)»

2 x ) /( : n = 0

'.I'<> find Il>c f ( )I;>l );<Ic ;i f w l i i c l i c l i c » i i c li l c i >elgy i s b e i » (< liber rite(l, = fi (1 — e

I) < x < /( : )(, )
we note that the overall result of the reactions (1) — (3) is tliat o » e f>. + gi
high-enei'gy p h osphate g r oup i s s p l i t o K , l i b e r ating e e r g s p cr c o » -
where </ = (f> + g>)h/s
traction site ii i <»ic cycle,. 'I'hc frc<lii<»icy w if h w l i i c l i .' I s i t e s ; » c p i < ,-
sented to each illsite is v/t, wlieie t i s t h e sepai ;itioii o f t l i c A s i t e s
<v < (): », -

. .
-
- ' -'- (1 — c ') e' .
along the acti n f i l a m ent,. T h e a v erage, number » f ' t i n>es eacli >I/ si f<> J'> -I- gi
enteis the cycle of reactions per second is tlierefoi(
'I'liese. relationships bef,ween», aiid x are plott ed, over the whole range,
,«' = — «««
« in 1rig. ( for f our v a h ies of' V. kor r e a s ons which w i l l a p p e ar l a t e r ,
— 1— »)(I,>,
/ J f(
f(1 — n~)(I/,'« » i
~
~ ~ ~ ~ I ~

/. (/,/(/', I !/,) is taken as 3/10 a>id g,/(f> + g,) as 3 010.

'

.«=-"

l»sci I ir>g these fo> m«lae, in equatio» (.")) and evaluating tl>e integral,
'I'li(', t»f al )' «>tc <)I <',i)(>1«y l)b< >':<I <oli I)<.i < iil» «. .c»I »i>< I i«c»I » i i l s<;I<., / (.',
w«'. )bf;ii» :
Is I I>(<1'(>l()l'(', gl v('I> I)v ;
'
; » (( I ' /' - - - »(.( .
'

/(,' J / ' (I ».) <I>r .

(!/) I
/> I (/>(''
.

'/'>-
/

who>'e >», is Il>e iilil)>h(.>»I )I/ sit(;s pcr c<ibic cci>tii)>elise of »i«sclc. W lic» I ' =-- 0, this gives thc " m a i n t enance heat" r a t e, J"o, as
'I'(1 f»)(l I ,h c I < » s><»1»1 I' ll( » » I s » I<' a s s » » 1( I «hl>I I I><', cl;>sl lc <'I<',ii)<'.ii!,
,/ ig 1
obeys Hoow> s hiw w i t t> a stiff'ness /: dyne /c»>. T li e average val«e ()f' )ne. -

tl>(', w«>'k (lni><.,'>I, or>< >>>y<)si>> sif<c as»i>(' a(',Ii» siI,<. is <.;i>'ried p;lsf, it l>y 2/ f , + gi
I I><', sl)»i I < )iilig«»l' I I)(, »>iiscl< is I holi wl>il« f,lic "cxt>'a i">f(>»l' (>»ergy libel;if ioli" / (" ( — /'(— / ( 'o) is

((/..v ( I,>, /( f' I'

/(," — »(e. -
-

.
'

- -

.
--(I — e ). .. (10)
/
,

2/ f l -I- gi
»s I
 %1 lr S('I, I.' S ' I ' u tr ( ' 'I' ll' ll I; 4 N I) 'I' ll I',() I( I lr S (> I' ('< > N 'I' ll<<> (''I' I <) N A I I V I ' O ' I ' 111'lg I S I " ( ) I'. 'I' ll l l i <1 I':(! ll A N I','(ill O l r ( 'O N T R A C T I ON

10 tltd the rate of eloing mechanical work is

n
08
06
V=O
04
'1'he. late of libe l'atio» of heat is E — P 1'.
02
-15 -10 -0 5 0 05
x/h f V. 3. Comparison nri thHil l 's equations
10
n To fittd out w h ether equations of these forms can represent the actual
08
b ehaviour of m u scle, we may see how closely they can be m ade to f i t
0.6 the relationships shown by A. 1>r. Hrf.f. (1938) to be obeyed by frog muscle
V =0 1 V . „
04 <luri]tg tetanic stimulat ion at O'C. T h ese are:
02 (1) The r at e o f l i b e r at ion o f h ea t i n c r eases linearly w i t h s p eed of
HI)ol tening (constancy of shortening heat).
-1.5 -10 -05 0 05
x/h
10 10
n
08
06
V =0 2 5 V
04 08
02
-15 -10 — 0.5 0 0" 10
x/h L
10 <)> 06
n
08
06 0
V= V
04 -
D 04
02
<r)
-15 -10 -05 x/h 05 10

1"ig. 7. V a r i a t i o n <>f rr (1>rnl><»tio«u f Hi t<a Ht w l ri< h lir>l( H I>< two<a> a< trr> <«1<I 02
rl)1'os«i a l ' e i l l ( ' s i s t <'n('c) vrrt I> <e (11osl t lon o f . I H l ( c n h l ( 1re I <> « I r « I <
I >r ««r 1
1H>sit ion of 1]f s i t e), for Ih e st e(uly s t a te in i s o r nef ric < on(nrr ti<>r>(r(>]1) r<r><l irr
Hh<>rter)r»g Ht. I hn «' l r f f < r< 1>< HIH'«IH.

>((I))]1(),I'Iy , <><I<];).(.]<>]) (Ii) I<>]' II)< (,( ))H ]<>)r I>« r<>r)l< H : 02 04 06 08 10
Tension
a<s/,' /', /<e
I I'ig. f(. .Relationshif> l]etweon sl>ee<1 of shortening and t ension. C o ntinuous
"/ /'
I </, l ir)c: I l l ] . 1.'s chara<>tcristic o<fuation w i t h II /Po = $. Circles: equation (11).
()nlrr>at<'., Hl>(>c<l <>I' Hlr<>rt('r«>rg HH a f r n <'.lier> Of V a l u o «l . « n l o a d o d t o ( a n u s
l ht; I n r t.'(Il l ) I I I) ) 6 ' (>I'k (1<)I)(' )) ) ) (' v( I< ; <I <>t« H I ( <! ]H /,/< /c '; ( I (» ( > I I ) ) r'<f I) I H r lhsc>HHH,, to«R>on HH rl f>'a(',tie>1 of val«c i n i s o l n o t r i c t e t a n u s .
bV I<', w('. I))tv(' :
( 2) Tile t o t a l r a t e ol' eltergy l i b e r at io n ( l i e at + work) i ncreases
1)<s)o /]
. (I (.I, 1,}" r') I linearly as the load is reduced below the isometric tension.
,'

./, By combining t h ese relationships H n.z, obtained his " c h aracteristic

equation," (I' + a) (V -}-/)) = constant , w h i c h h e f ou n d t o agr e e
') 87
 A 1 t<S(" I( I.' S'I' I( t> ("I' I( I< I; A N » 'I' ll I;<) I> I I: S () I' ('() S 'I' i(A ( ' ' I ' I <) Iv A I ! Y T(01'l l I: s rs F o lt ' I ' Tl I : T > I:(' ll A N T s l>t O F C O N T R A C T I ON

excellently w i t h t h e d i r e c tl y d e t e r»>i»ed I'orce-velocity c u r v e . T h e 032

c onstant (t w a s f o un d t o b e appro
ximately
one-quarter of Y< ), t h e
isometric tension; /) is necessarily equal tu a/Pe >»ultiplied by the speerl 028 0
of shortening under zero load.
I nspection of e q u at ions (g) and ( 12) shows tl>at Lve have only t ) >u oc 0 24
(
adjustable constants left f o r f i t t i n g o>» equations (o H TRT. s relation-
ships (with a /Ye = ~t ). They are 0
020
L0

><',/ > I —
!/ ('1 ,/, , '!/, 0'16
(>»( I
( 0
(/„
0 12
032

028 008
0
0 04
L . 02 4

>, 020 02 04 06 08
Speed of shortening
016
I'ig. 10. Relationship bet,ween rate of heat production and speed of short-
((-
0 (,ning. St raight line corresponds to a constant heat of shortening (as found by
0 12 H<»..) vvith (( /V» .= $ and maintenance heat rate = ar); ci r c les from equations
0 (!>) nnd (I' ) . O r d i nate scale as in 1'ig. 9; u n it y o n abscissa scale is Vm(>„, the
008 speed of shortening in an unloaded tetanus.
0

004 032

c 028
02 04 06 10 0

Tension L 024
1(ig. 9. I t c l a t i onship bctvv«r 0 total rate of energy lib( ('n(ion (bent, + <vorl<) nnd
tension. Straight line, fro>u 11»,>. s equations with « //', ) —,' sud mainternun « o 020
heat rate = <((). Cir(.I«s: f r nn> equations (9) nnd (11). On abscissa, scale. unit>
is 8», th e i s om<'.tri( t e n sion ; o n o r d i n n t e scale, un it y i s t h ( p n ) <lu( t / ' » 1~»„„.
0 16
((-
I he I'atto !/>//I l»>s also tu l )c cl>us(>» so (Ls I u g>v('. I I>(', »>(Ll» t('n(lt>c(> I>("LI 0
0 12
>;Lte:L v(>l»(, c<>r ><;sl)o»<li»g to I I»:(, I'<>t»><l <;x»<;I i»><.»(,;>lly; HI>,I, I'<»»><I 0
I I»t(, il, was »,I)u»I, (><I»n,l (,u «/).
'V»',ll at><l <'»'>'<»' sl>uw(',<I tl»ll, I;L>r;L«>'«,:»><',» I <,u»l<l I>c ul>I>l»>c<l. I>y 0 008
0
»»LI(>l>g 'I(' /<' ) 7• () </I/(/> ,'/() '
, 'I/ I (i, ; L» d < //(/>
9 -I- </>)
004
'.I'hes(> «ive I ' u u„ . -

-I (1. (/>, s<> t I»: t ( /) is <)<I»:>I t<> Hlr,l,'s /); (1 > (y ; > I so
»>>Lk(; t l>c 1»alr>t<;»>L»c<'. I><.;a( I'(Llc b(.'>L>' tl>(: <(o>'I'cc( pr'upo>'(>o>l (I/I b) I <)
02 04 06 OB 10
the I)roduct P o V mn~. 'I.'h(> 'dcg>ce (>I' success ir> l» at cl>i>tg H t b t ,'s
t clationsl>ips c>L>t bc scc>t I'>o»> I>'igs. S, !), IO. ;Lud I I . 'J'h(> der i>ltiot>s Speed of shortening,fraction of V<n«
I 'tor» l>yperl)olac i» I ('igs. 8 ; L»d 1 1 , ; L»(l I' n»» s!,»; igl>t li»cs in I('igs. !) I 'ig. I I. I u ( al <i«»ship I>( tw«<n( t«tnl n<te of energy l i b eration an d speed of
and fO, ar(. probably ru)t >>tuel> g>(utt<;I I I»:r> I hc cxper i>ru,»(>tl e> rur OI s h«(tr ning . ( . ' o n t i n u uu s « u r v ( (hyperbola) d<nived f>om Hrrl ' s relationships,
<vl< h « // » ( nu(I n>nint( nnnc(> beat, r n t « = <6; < ircl«s f>om <.quation (9).
the obser vatiuns o» which I-ill ,l. I>as(.<l 1>is >(,Iatio»ships. (>rdinnt«scale ns in I (" ig. 9.
) q()
 M lr«<CJ« I«) STR I ? ( ' T I ? 1L1«: h N 13 T r f l «l (I R 1 KH ( ) I«' ('!( ) N T R A C T J C N
Although only t w o c onstants were available for fi t t ing H i d ' s
equations, and one for fitting the amount of maintenance heat,
arbitrary assumptions had been made at an earlierstage in making f
and g vary with x in the ways shown in Fig. 6. One or two other forms
o f these relationships were also tried. Wi t h f and g constant (instead
of increasing linearly w it h x ) in t h e r a nge 0 ( x ( /L ,H JJ.L's equations
c ould be fitted about as well as with th e system discussed here, but t h e
ratio (v /e had to be given a value of about unity. T his is not plausible,
as the three reactions that are postulated cannot all go spontaneously
in the forward d i r ection u nless tv is considerably less than e (wh ich is
a ssumed to be derived wholly front a change in free energy). T h i s
result was not much altered when the change-over from high f to high
g was shiftedfrom the point x = 0 to x = A/5. It can be seen intuitively
that, for agiven value of L%, the eSciency will be lower in t h ese
systems with constant f than in the one developed. here with f propor-
t ional t o x , b e c a use d u r in g s h o r t enin g a h i g h e r p r o p o r t io n o f t h e
a ttachments will be formed at small values of x (therefore contribut i ng
l ittle to th e w ork d o ne) in th e former system than in th e lat t er .
Another system, within the same general framework, which is of
interest, is one in w hich f a n d g v a r y e x ponentially with x . Th e
equations are:
e(L — h)/i
c(s — I«)/i
Force in elastic eleinent = p = p » (L „
1 — 0(
x ) h: f = 0, s o t h a t n o c o m b i n a t i on o c c u rs d u r i ng s h o r te ning;
g and p therefore need not be specified.
The interesting joint about this system is that it satisfies Hrr.r.'s
equations exactly. U n f ortunately it gives about 5 times too high a
value for the maintenance heat, because of the great overlap betweett
the functions defining f and g. M a t l t e m(Ltically, th is can, be overcotnc
i f g is allowed to become negative when x has values near tn h, lnlt t h i s
ls 1101«p rllllHHI1)1(') «Lt ally I ' ILt«( ! wllill()Ill«('xl I'IL «Lisisll Ill f)tl()lls, ILH ll I l t l p l l ( ! H
I«llc Hlt(till (LI I(l(tl(H I'(lV(tl'HlLI (Il I L I ' ('ILcti(Ill. wit icll g ( I C H ill 1 II (: f u t w Ll (I
d ilcction w i l l > l l l « r e l ease of a l a rge alnounl (>f ft.ee cltergy. Fo r t ilia
I'CILH(Ill> I 1alll(lvc l lla«l« ll« IH Il tl lit'()lll«ll,blc l«() He«LI<cll fill'tllcl' lor' Hc) teltt((H,
witliin the framework of the general hypothesis th Lt is under discuasio»,
whicll obey l i t t . t.'H cqualiutis exact ly , s i nce l ltiH p(Lrliculal Hystettt is
probably unique ingiving an exact agreement, apart from a "family"
of systctns th Lt ca» lie <Ibt;Litic<i froln i t 1)y t t lhnsforluations in w l t i clt
the r a t i os 13etweellj, < /, ILtl(11) al'0 (lit(lit'Lrtged;Ll, ea<;11 v;Llue of'. I,,; L ll<1
whicll lc(L(l to l « llc «s«LIIlc I'cl«ltl()IIH 1)(ll«w(l('ll Hpe(l(1()1 Hll()l'lcnlllg, t ( lttHI(III>
and rate ofliberation of heat.
«3 )( 1 )
A Ji YPO T H I i s l s 1 «'()R 'I i ll : M a o i r h N i s M o l ! ' C O N T R A C T J ( 3 N
IV. 4. Coneerrtrenceef othe hypothesis
IV. 4 . 1. Le n gtILewLng fo <LsfLJnnl<hte<l mn8ele
several interesting results coine out if one follows up the consequences
of this hypothesis. The first that I shall deal with concerns the tension
i n the muscle when it i s f o r cibly st r etched during t et anic stim ul at i on .
Hrr.r. (1938) found that there is a discontinuity in the force-velocity
curve at the point where the velocityreverses: the increase of tension,
above isometric, required to produce a given small speed of lengthening
is inuchgreater than the drop in tension which allows an equal speed
of shortening. KATz (1939) investigated this further and his curves
(fig.5) show that — dP/dV, the slope of the force-velocity curve, is
about six t i n ies greater for slow lengthening than for slow shortening.
Our hypothesis leads to a similar discontinuity, because during slow
lengthening n falls oK beyond x = h w i th a s pace constant equal to
( — )v/gi, while during shortening the corresponding space constant of
the deficit of n be low its steady-state value is v/(fi+ gi ), which is
several times smaller. The resulting changes in tension are propor-
tional to these space constants, but during lengthening there is also a
<lrop in tension due to the fall of n near x = 0 . T h e o v erall result is that
t,he ratio of values of d P /d Vfor slow lengthening and slow shortening
is f i/gi,which we have taken as 4 88. This fig ure is to be compared
with KATz's value of about 6.
As the speed of lengthening is increased, n becomes appreciable at
greater and greater values of x, and we are assuming that g rises in
proportion. Hence,the dissociation of A3I links becomes more rapid,
while on the other hand. there is less time for the links to be formed
because ofthe greater speed. Together these two factors set a limit to
the rise of tension; as the speed. is increased indefinitely the tension
approaches asymptotically a value Po(fi + gi)/gi, or 5 88PI with the
values taken here. This is qualitatively similar to the "give" or "slip"
whicll h appens when a muscle is stretched during a tetanus, at anyth i n g
1)ut a very low speed (Hrr,r,, 1 (J38), but Km'z (1989) found that the load
»c(«(1«:1 t<l (:<L(IH(lv <!ry r(Lpi<l lcngt)lcnillg w as only 1 8 P »
A qualitative explanation is also given for another phenomenon
(lescribed by K A Tz ( 198 (J, fig. 7). A muscle is tetanized and allowed
l <I shorten under small load until it reaches a stop; then, before it has
lla(1 time to develop much tension, a load about equal to th e isometric
tension at the shortened. length is applied. The muscle is considerably
st etched,
I and then shortens again to approach the stop asymptotically.
'1'he explanation would be that during the initial rapid shortening the
lotal number of links in existence is small, as shown in Fig. 7 (p. 286).
l f tile load is applied before the number of links has had time t o
increase, it will be more than they can hold, and the muscle will "give."
291
 Mu s C L E N T R IJ < ! 'I'll ICIl A N l r 'I' ll ll<) I< I I!s <I I ' « ' ) N 'I ' I < A C ' I 'I O N
A limit to the quick stretch is presumably set by the fact that t h e
muscle is being brought to greater lengths, at which the isometric
tension of which the muscle is capable is also greater.
So far, the system has accounted well for th e behaviour of a i n uscfe
t hat i s s t r e t ched d u r in g s t i m u l a t i on . B u t a s i t s t a n d s i t d o e s » o t
predict correctlythe amount of heat that isliberated. ARRo TT, AURERT
and HILL (1951) found. that during slow lengthening the rate of evolution
of heat was increased by an amount which was lessthan the equivalent
AURERT (1951) found that
of the work done on the muscle; AERO TT and.
the total rate of evolution of heat, including the heat derived from the
work done, might even be less than the maintenance heat rate during
an isometric tetanus. On the system we are considering, the rate of
evolution of heat (apart from mechanical work done) should increase
with speed of lengthening in exactly the same way as the total rate of
energy liberation increases with speed, of shortening (equation 9). This
d iscrepancy could be eliminated, at l east qualitatively, i f i t w e r e
assumed. that at the larger values of x the AM liinks were broken not
by reaction (2) (p. 288) but by the reversal of reaction (1), which does
not involvethe splitting of a high-energy phosphate bond. There is
no difhculty in principle about this reversal, of the kind that prevented
us from assuming a reversal of reaction (2); indeed the equilibrium of
reaction (1)is bound to go in favour of the dissociated state at su%-
ciently large values of x because of the large amount of energy needed
to bring 3I to the position where combination can occur, and the
consequent rarity of collisions between A and aV.
IV. 4. 2. Unloaded shortening
It has been assumed tacitly that the only factors limiting the speed of
shortening are the applied load and the resistance generated by those
l inks which are still connected after x has become negative. For a
g iven speed of shortening, the second of t hese terms will b e p r o-
p ortional t o t h e n u m b e r o f s i t es w h ic h ar e a c t i v at ed, as also is t h o
t ension generated b y t h e c o n t r a c t ion p r o cess. I f t h e l o a d i s z e r o ,
therefore, the te»sion generated and the inter»af I esist<L»ce to slr<rr tcrr.-
irrg will booonro o<]<r<rl «I ILafro«;j <rf <Ill<<et«»ing wlli<,tl rr< I»<lot!o»<h',»1 <r(
t he number of ' sites t ha t a r e a c t i v e ; i n o t h e r w o r d s , t h e s p eed o f
u nloadod shortening is independent of the degree of activation. In t h e
real case, no doubt there are other 1unds of resista»co to shortening
w hich do no t d e crease proportionately w i t h t h e d e gree of act i v a t i on ,
so that the speed of shortening would fall off when the degree of
activation becomes very small, but nevertheless this argument does
s how that t h e i n d ependence might h o l d , w i t h i n e x p erimental e r r o r ,
over alarge part of the range. This result, which would probably be
true also for many other types of contractile system, suggests t) lat
<7<1g
A 1l V J.'OTI< Mr<IS 1'OR, Tl l z M E C 1 1 A N I S M O P C ON T R A C T I O N
caution is necessary in interpreting the rapidity with which speed. of
shortening reaches its maximum after a st imulus as evidence that
activation is c omplete equally early ( H n r , 1 9 5 la ; AR E OTTand
Rrrc111E 1961b ).
IV. 4 . 8 . A c ti<ration and relaxation
The concepts ofactive state and degree of activation, introduced by
A. V. Hnz.,have been very fruitfulin reducing a wide range of pheno-
mena in muscle to dependence on s, single variable. A muscle is said
to be inthe active state when it is capable of shortening or developing
tension; during Ml activation it obeys Ha@'s characteristic equation.
The degree ofactivation at any instant is measured. by the tension
which the muscle can just hold without either shortening or lengthening
(Hn.L, 1949c). Hzr.Land others have shown that to a large extent the
time course oftension in a twitch can be explained by supposing that
the degree of activation rises from zero to its maximum very quickly
after the stimulus, stays at its maximum for. an appreciable time, and
then falls away gradually to zero. The relatively slow rise of tension,
and the failure oftension to reach, in a twitch, the value that it
achieves in a tetanus, are explained by the presence of a series elastic
e lement which the contractile elements have to stretch by a 6 n i t e
amount inorder for the tension to appear at the tendon. Relaxation is
explained. simply as the disappearance of this active state (Hxrz„1958b).
O n the hypothesis that we are discussing here, activation in t b i s
sense involves two distinct steps. The 6rst consists in allowing reaction
(8) (p. 288) to occur; t hi s reaction is the removal of the phosphate
groups which during the resting state have been preventing the A
elements from combining with 3f . Th e s e cond step is t he a ctual
formation of the A—M links. Nothing has been said so far about
reaction (8) except that during a fully developed tetanus it is so fast
as not to be a limiting factor. If we assume further that it is complete
practically instantaneously after a stimulus, there will still be delay
Irr the development of the degree of activation as de6ned by HI LL,
boc;t,usc the muscle can only hold tension in proportion to the number
<r fA iV links that have been formed, and the rate of forma tion of th e se
links is set by the rate constant f which is flnite and is related to the
maximum speed of shortening of the muscle. The same distinction
arises in relaxation: e ven i f t h e d egree of activation fell t o z ero
suddenly because reaction (8) was stopped, the A3I li n ks already in
existence would persist for a finite time, their number decaying with
the rateconstant g. So long as any of these links persisted at the end
of an isometric twitch, there would still be some tension, but the muscle
would not becapable of continued shortening if the load was removed
because nonew AN links could be formed.
 i)r IraOL E S ' I ' R I" ("I'I( R I!I .\ N I> ' I'Ii il u R I ><la (> I" ( ' ( > iVT R 4 ("I' I <> N
Heaction (3) waa chosen somewhat arbitrar 'ily on p. 283 aa the one
. be several times longer than the time constant for forming them at
that was inhibited during the resting state, and it wa s mentioned
there that inhibition of reaction (1), the actual formation of the links,
might equally well be the means by which relaxation was produced.
Even if this waa so, there would still be two steps in activation, namely
t he removal of t h i s i n h i b i t ion and t h e f o r m at ion of t h e l i n k s : ever) if
the first of t h ese was instantaneous, the second would only t ak e p l ace
with the rate constant f. Short of postulating a dual nature for the
initial step, I h ave not been able to t h ink of any v a r i ant of th e general
hypothesis which w o ul d n o t g i v e t w o s t a ges i n b o t h a c t i v a t io n a n c1
relaxation.
If, t h en , t w o - stage activat ion an d r e l ax ation ar e n ecessary conse-
q uences of th e h y p o t h esis, it i s n a t u r a l t o a s k w h e t her t h ere is a n y
experimental evidence for either or both of these phenomena. O ne case
where such evidence exists is in t h e i n d i r ect fl i gh t m u scles of certain
insects and the t y m ba l m u scle of cicadas, where PRINGLE (1949, 1954)
has shown clearly that two distinct kinds of activation are involved.
In their normal activityin, site, these muscles contract in an oscillatory
manner at a frequency very much higher than the frequency of the
action potentials in t h eir f i bres. I n t h e c icada muscle, I R>Noi.s shows
that a single action potential pro duces an active state lasting between
50 and 100 msec, whicli can aunnnatc w i t h t l >e eB'ects of succeeding
s timuli . & h e r r t h e i n u s cle i s a t t a c hed t o a l e v e r f o r r e c o r ding i t s
contraction, ari ordinary t w i t c h o r t e t am>s results, biit i f i t i s i n si t > (,
it performs a series of cont ractions at i n t e r v als <>t' 3-10 msec so long
as the active state is at a s u tBcient level. E a c h o f t h ese contractions
causes the tymbal (the "drum" with which the cicada makes its song)
t o click f ro m a n " , o ut " t o a n " i n " p o s i t i on ; a b o u t 1 m sec after t h i s
contraction the tymbal clicks out again, stretching the muscle. Clearly,
some kind of de-activation must have occurred as a result of the shorten-
ing, which allows the outward click to occur; this must last for only a
very short t i m e as the muscle contracts again a few m i l l iseconds afte>
t,he outward click and repeats the cycle; up to 8 of these cycles may
o ccur. within 4 0 mace or a o a f t e r a s t i m u l u s w h ic h p r o d uces only a
Hir>gl(»>(',ti<»> p<>le»tial. O >i <»>r J>yl><>tJ><
isis, tJ>(; cll'<;ct (>1 11>c aetio>i
poterrtial might be to remove the inhibition of reaction (3) for say
50 i»soc, wliilc sh(»t>cuing might c a use <liaaoclation of' tlie A. 3t l i n k s ,
wh>cll wollld tJ>ell »eed >l cei'ta>11 tl>1>c t'0 >'cfo>'I». The >Blpoi't>a»t 1>(»>rt )
Jiowever, is t h a t t h e s e » i u aclea — adniittedly v c i y s 1>ecialize
(l o>1(>s-
-
s how two qu ito (listinct k i i rds of a«tivat io» .
In ordinary muscle it might be expected that, if these two stages
e xist, they w o u l(1 lre easier t o ( l i s t i irguislr duririg relaxatioii t l i a n « t
the beginning of a contraction,since it waa shown above that the
time constant for breaking the A3f li n ks in relaxation ( — 1
/g) should
'>() 4
A ir YFOTH E S I a F O R T H E M MO H A N IaM O F C O N T R A C T I ON
activation ( 1/f). In a n i sometric twitch, this two-stage relaxation
would show up by the active state (detected. for instance.by the ability
of the muscle to redevelop tension after a quick release) falling to zero
while there waa still considerable tension remaining. This point does not
seem to have been submit t ed. to direct experimental teat, bu t s everal
p ublished results suggest that muscles do behave in this way. F o r
example, inthe contraction shown in flg.1 (top curve) of a paper by
HITGHIE and WI LKI E (1955)the degree of activation has fallen to 7 per
cent of its maximum value at 330 mace after the stimulus, while the
tension is still 90 per cent of ita value at the peak of the twitch, and
74 per cent of the isometric tetanus tension.
lt also seems di6icult to explain some of the quick stretch phenomena
described by KATz (1939) without distinguishing between two steps
in. the activation process (cf. pp. 291 and 308).
IV. 5. Size and nrjrnber focontraction aitea
IV. 5. 1. Range fomor>enrent of aide-pieces
A rough estimate of the value of (rr, the largest displacement at which a
side-piececan become attached to an actin fl lament, may be obtained
as follows. On p. 288 it waa shown that the quantity $(= (ffr + gr)I>/a)
caine outto be equal to HE'LL's b; hence
k — ba/(fr q gr), (13)
Now gr/(fr + gr) waa set at 3/10, in order to give the right amount
of maintenance heat ; h e n c e 1'r= 3ba/16gr. b and e a re known (for
frog muscle atO'C), and an estimate for g~ can be obtained from the
decay of tension at th e end of an isometric twitch, accepting pro-
visionally the interpretation given in the last section. The same curve
in RnrHrE and WnaUE's paperthat was referred to in that connection
givesthe time constant of decay of tension as about 150 msec at about
,>00 msec after the stimulus, when the degree of activation appears to
have fallen to zero. This time constant should be of the order of 1/g,;
t liis is no t a n e x a c t e q u a l it y b e c ause g v a r ies w it h z ( s o t h a t t h e
tlicorct,ical limo course ia not, exponential ), and only reaches gr when
x = h. H ence 1/gr is likely to be less than 150 mace; we might take
100msec, making gr = 10 aec-r. No w H xr,L (1938) found that b i s
about dI acc-', and a is about 2 5 p.; i n serting these values in the above
equationw<' obtail>
3 x ( x 2- 5 p
h= - -
= 156A .
10 X 10
This figure is subject to considerable uncertainties. Thus, the values
taken for b and for g, were obtained from difFerent frogs, and the
 Mrrs(>LM sT R rr<'.TITRIL AN I> Ttr z <>nr>'.s <>I « '>N I'R A ( ' T l < > N
estimateof gi w as in a r sy c ase very t o u g h; al s o t h e v a l u e f o r t i l e
ratio f,/g, was obtained on the somewhat arbitrary assumptions ((L)
that the whole of the maintenance heat is derived from the breaking
of A3f links at values of x between 0 and 1>, and (1>) that no links are
broken by a reversal of reaction. (1). None the less, the value is one
that would fit i n w ell w it h th e at tractive possibility that th e side-
pieces are placed at intervals along the filaments equal to the 415-A
period which has been observed with X - r ays (BzAR, 1 945; H. E .
HUxLzY, 1952, 1953b) and i n t h e e l ectron m i ci'oscope (HALL, JAKUs
and SOHMlTT, 1946; DRAPzR and Hor>oz, 1949 ).
IV. 5 . 2 . D i s t ance 1>etu>een snccesaL>>e A sites
O n p. 286, a f o r m ul a f o r t h e t e n sion d u r in g t e t a nic st i m u l ation w a s
derived (equation 11). P u t t ing V = 0 , w e obtain for th e isometric
tetanus tension
2na>U fr
...(14)
2l (fi + gi)
>o was set at $e, and f,/(f, + gi) at 13 /16, so that
1 = 0 305>2>>se/P„. ...(15)
Valiles foi' the quar>titles oil tire 1'Ighti-h;>nd s>de of this eqilatioil nlay'
be obtained as follows, s i s 2 5 p or 2.5 X 1 0 4 cm; Po for f r og muscle
is about 2 kg /cmm, or 2 X 10~ dyne/cm~. 2n, the number of JI si t es per
c ubic centimetre of m u s cle, may b e p r o v i sionally i d entified w it h t h e
number of myosin molecules in the same volume; this may be calcu-
lated from a concentration of 8 g /100 ml. and a molecular weight of
8 40,000 (Wzrrzz , 1950) to be 5 7 X 1 01%. 0. If the heat of hydrolysis
of the high-energy phosphate group is taken as 10 kcal /mole, then e is
7 X 10 13erg/ molecule. Inserting these values, we obtain l = 153 A .
T he interpretation of t hi s result is complicated by th e fact t hat i t i s
close to the estimate we have just obtained for h. Equation (6), froni
which equations (11) and (15) were derived, assumes tacitly that I i s
consi<lcrabty greater t1»L» h„H<> l,l>at; 0>Lol> 2V Hit o is >Llways free 1'><>ni it,»
1>L>>t)>Lttr>Lot>I>10» ti to >» I .'1 l>010f0 ll>0 »0><t A 1>1'08011ts>liscll 101' co>nb» i>L-
tion. I f l wa s r e a 11y smaller t h n n h , t h c ( » L1(.
irbLti<>I> wo have gone
through would probably give the value of /e, not of. l; the relationstiips
l>et woon force, velocity and 1>0>Lt productio>i would also be modified it'
lwas not appreciably greater than h. We may conclude either that 1
is c<lual to or sinai lci l,ll>L>i 1>,Ill whlcli 0>Ls<> i>lie ligure we have obtainc(1
i s <L confirmation of.' tl>c otl>or ostimat>o of 1> but the for>nulae for t l i c
force-velocity relation, etc. are no longer exactly appropriate, or else
that 1.is about 150 A and h, is appreciably less, say 100 A, which woukl
29t>
A II Y I'AT>i >;srs I<o I< 'I' ll ll M z( l riA NIS M o l ' oo NT R A (>TIo r<
probably not betoo small a value to confiict seriouslywith the earlier
estimate.
I V. 5>. 3. 8p<rcr',2>gs expected on st>'2<ctu>'nl g>ou>L<ls
I<:stimates of th e spacings of m y osin and a c ti n m o l ecules along t h eir
r espective filaments can b e o b t ained from t h e q u a n t i t ies of t h e p r o -
teins present, their molecular weights, and the arrangement and spacing
of. the filaments deduced from H . E . H U X L z Y's X - ray and e lectron-
>nicroscope observations. These calculations have been made by
HANsoN and H, E . H U X Lz v (1955, p. 253). For the myosin filaments,
a ssuming that t h ere are six m o lecules abreast (one facing each of t h e
s ix actin f i l a ments w h ic h s u r r ound t h e m y o si n fi l a m ent) , t h e y f i n d
that t h e l o n g i t u d inal s p a cing c omes ou t t o a b o u t 4 0 0 A . , a g reeing
remarkably with the well-known 415-A period seen with X-rays and
the electron microscope. Each actin filament is surrounded by three
myosin filaments; assuming
therefore three actin m o l ecules abreast,
they calculate a longitudinal spacing of about 130 A. This is close to
the upper limit that was obtained in the last section for the distance
between successive A sites with which any one M site can combine;
it, would be very natural to identify t his with the spacing of actin
>nolecules <Llong a filainent.
IV. 6. DL scrrssLon
At the outset, it, must be emphasized that the agreement which has
been achieved with some aspects of the known behaviour of muscle
is not to be regarded as grounds for accepting the scheme which has
been put forward. There islittle doubt that equally good agreement
could be reached on very different sets of assumptions, all equally
consistent with the structural, physical, and. chemical data to which
this set has been fitted. The agreement does however show that this
t ypo of mechanism deserves to be seriously considered, and that it i s
worth looking for direct evidence of the side-pieces, and of the localiza-
tion of enzymic activity, which have been postulated.
()uite apart from the possible value of. this scheme as a working
l >yt>othosts, several ol' th o r esults are o f m o r e g eneral i n t erest. T h e
1>ruposed mechanism may be described as cyclic, in the sense that the
riumbor of sites in a given condition is not affected by shortening:
Oacli side-piece goes through cycles in which it combines with the actin
filament by one reaction and isseparated from it by another. The
final states of the side-piece and of the site to which it was attached are
the same as their initial states; the only changes are that the muscle
has shortened, an energy-rich phosphate bond has been split and. work
may have been done. The mechanism may be contrasted in this respect
with any of the theories that postulate folding links in series: in these
' 't 297
 Mi>SCLI< ' <'I'l<,ir(" I ' I ! 'I<i<> A Nr) ' I ' l r I<« I<1 ES <') I( (!<)'N'I'il A ( » I ' I ( ) N
the >lumber of l i n k s i n t h e f o l ded condition i n c reases as tile m u scle
shortens. M e chanisms based on th e sliding h y p o t hesis are not n eces-
sarily of the cyclic ty pe : o f t l i e t h ree classes of mechanism de6ned on
p. 270 (2) and (3) are cyclic but (1) is not.
I n a c y c li c sy stem, w or k m a y b e d o n e several t i mes a t c a d i s i t e
d uring a given contraction, wh ile in o t her systems net w ork ea» o n l y
be done once. I f t h e w ork per cycle at one site in the first case is of the
same order of m>lgnitudc l s the wo> k pcr link folded iii the 8<,c<>i<d (e.«.
because both are related to the free-energy roleasc on hydr<>lysis of' ari
energy-rich phosphate bond) the number of sites per. unit volume will
come out smaller in the cyclic systeins than in others. T his is iIlustrated
by the f'act thrlt t h e m o lecular weight o f t h e a c t ive unit o f >ny()siu is
assumed here to b e 840,000, while botl i HxENT-GY<>>M Y> (1!)5'.I, I ). 3!i)
and POLIssAR (1052d), assuming non-cyclic syet<8»is, arrive at f i g ures
of around 40,000.
Another point is that several of tlie general questions that have been
asked about muscle (for instance, whether energy-rich phosphate is
split during contraction or during relaxation) may lose their. meaning
in connection with cyclic mechanisms. Thus, in the system developed
here, phosphate ie split off, by t h e same reaction, (]uring 1)oth cont>.ac-
tion an d r e l a x at ioz>, Him ifa>iy, t h e q u estion d i scussod by M C RAL>.'8
ef, (>l. (1055), whether contraction is produced by the combination or
by the splitting of ATP, has no answer on a system of the kind discussed
here: th e im m ediate cause of tension development is tl i c ; l c t ual fo> I»;<,-
tion of the links between actin and m y o sin.
I n t h i s s y st em , a s i n P C L zssAR'8, HE'LL'8 relations b et ween l o a d ,
speed ofshortening and heat production are brought out as approxi-
m atione. T h i s i e p e r h ups r a t her i m e atisf'yfng, but, it, docs a c t ; l s ;l
r'e<i)>i>der' t liat I hcories need not b e d i scarded simply b ec<luse they (h )
not; 1ca<l exuctly t o t I >e mathematical f<nrui<1;ltion tl iat w u s g i ver> 1>y
HILL, 80 long as they fit th e experinielital data adequately.
A I'<;:ll i)rc <)f 8«)»<; g<,r»:I'al i»I<)n)NI, is I)i«u g li t <>i)I, I)y ( « riei<I<,r i)>« I h<;
secor>d of HE'LL'8 relationships (p. ' >07) in a shglitly d i f ferent f or »i . I t
i s i>su;lily c x p n s sed l>y 8:lyiiig I ,h;lI, II » t <>ISI <.stra i ; l t «
; >f ('I»;>gy
)r)II«i) (I)i <;~(:<)Hs «I' I,Ii<)»);)ii ) I ( ;i i ; u » ;(; I» )»I, ) i»(;r(;;ls())< Iiri(:;li l y ; l s I , I « ;
l!1)(,
I<>ud is i<educed below thc is«r>»)t,ric t(:><si«r), I>cii>g cqu ll tu 6 (P O — /'),
I I w<) siil)st I'tnt( I'«I' 1 'I h(l vr) I <io gr v(ll) I) y I I I I I > 8 (lhirr'il( I < I'ISI>I(' cqurlt I() Ii,
this becon>es 1~(P„ + (I ) V/(V I- I'>l. Th»8, a~ t h(( speed of eh<))t(»ir)g
i»ci'cu)rcs, the 4«tal I i l t c « I e n ergy l i b er)l! i<»i tisce rrlpid l y ; l t f i r st, <i>id
then more slowly (cf. Fig. 11). This shows directly that the amon>it
(>f (!1»)l)l>t;Ill (!hri»g() I)()r' u»II r l » » ) u» I « I s h « l ' I ('.»)r)g I s » « I r l ( ' « )>8!rl»I ,
but I'z118 <lH tlic, 81)ccd «I' sh«rtcriirig r is<;8. 1) . fyf. N i<r<»I<AM (I!>50,
p p. 4>f — 40) drew att ent ion t o t h i s p o i n t , c o n cluding t h a t i n d i v i d u a l
sites were active more than once during a contraction if it were carried
)() <~I
O TII E>< I ' I I E N O ' M I '.WA I N M U S CL E
out at low speed, and that, even if ATP breakdown were associated
with restoration of the protein chains, it might occur during the con-
traction phase, bringing the sites into a condition in which they could
react again, as well as during relaxation. In the system described. here,
the fall of energy liberation for unit shortening as the speed is increased
is provided for by giving a finite (as opposed to infinite) value to the rate
constant f for the formation of the links: ae the speed of shortening is
i ncreased, there is il p a r a llel r ise in t h e c h a nce t hat a p a i r o f A a n d
.Il sites will pass each other without any c hemical reaction taking
place.
It i s n atural t o as k w h ether the mechanism proposed here for
striated muscle could account also for t h e contraction of smooth
muscle. On g eneral grounds, it is t o b e expected. that th e inechanism
isfundamentally the same in both types, eo that it would be unsatisfac-
tory to postulate for one type a mechanism that clearly cannot exist
in theother. Not enough ieknown at present about the submicroscopic
structure ofsmooth muscle to make a de6nite statement either way,
but there does not seem to be anything to exclude the possibility that
smooth musclecontains, in a much less orderly arrangement, 6laments
which aremoved past one another by a mechanism similar to that pro-
posed here for striated muscle. The absence of any marked change in
the wide-angleX-ray pattern (AsTRUR Y, 1947) and in the strength of the
intrinsic component of the birefringence (PzscHER, 1944) when 8mooth
>iuiscle is stretched or shortened over a wide range, do indeed stiggest
that the filaments move relative to one another wi t h out m uch i n t ernal
r earrangement; a n d a s l on g ag o as 1036, BCELER suggested that t h e
mechanical behaviour of smooth muscle could be more easily explained
1>y assuming that contraction took place by relative movement
between the molecules, than by changes in their shape.
V . OTHER P H E N O M E N A IN M U S C L E
Tlie l i y p o t hcsis of ' m « s cular c o n t r a ction se t o u t in t h e p r e c eding
sections was originally developed as an attempt to 6 t t o gether the
available informatio» <>n (I) muscle structure, (2) the relationships
I)ctw(<ci) shortc»i»g, le»r<io>) und heat liberatioii, and (3) the outstanding
I'ucts concerning the interactions of actin, myosin and ATP. T h ere are
of course many otherphenomena which may provide important clues
to the mechanism of contraction and which will have to be explained
hy any theory wliich ; l ime at completeness. In. the following para-
graphr, some of these phenomena will be discussed in relation both to
t Iic i(lorl that, Ie»gtli changer< take place by sliding of actin and myosin
filaments past one another, and to th e particular hypothesis which
has been developed here. Possible new interpretations of the data
emerge in several cases.
 M i f ia u fr lrr ST II I l ( " f ' l l l l Z p N I I ' I' ll lrl(I I( l I r' N ( ) I ( ( l( I N T I I r ( ( « l ' I ( I N
I. 4<'u('iy clucnye~ in u l((Iilcj(,
Several physical changes are known to occur very early after a stimulus
is applied to a muscle, all being apparent during the latent period
before the rise of tension or shortening of the muscle begins, and being
complete well before the peak of the twitch. Th e principal ones are
the following.
(1) A small drop in tension (the "latency relaxation" ) precedes the
main rise (RxUH, 1022; ScH<zzzz and Gopzzzr, 1037; SzNDow ,
1944, 1947).
(2) Th e t o r s i onal r i g i d it y o f an i so l a t e d f i b r e i n c r eases (i'3TEN-
KNUDSEN, 1053).
(3) An i n c rease in th e h y d r ostatic p r essure to w h ich t h e u i u scle is
subjected c a uses a n i n c r ease i n t h e t e n s io n t h a t i s s u b seclue»tly
developed (" alpha process," 3RowN, 1034, 1936, 1041).
(4) The resistance of the muscle to passive stretch begins to rise
about half way through the latent period (A. V. HiLL, 1050b, 1951b).
(5) The rate of heat production rises rapidly to its maximuin about
half way through the latent period (A. V. Hizz, 1940b, 1950a, 1963a).
(6) The amount o f l i gh t d i fFracted by t h e s t r i ations decreases
(D. K. Hizz, 1063).
Prob(l,bly alf of tficsc cfiwigcs hcgili ;i l a bout t fic sa»ie lime, b(it tficre
is a good deal of uncertainty, portly because parallel measureuieuts
have been niade in only a few cases (1 a,ud 6, D. K . H 7I,L, 1049; 4 a i i (l
5, A. V. H 77.D, 1050a,b ), a»d partly b ecause t1ic tim c r c solutfon iN ilol
good enough in some cases (2 and 3) for precise comparisons to be made.
The later part of the time course is obscured by other changes which
accompany the contraction itself, except in cases 2 aud 3.
V. 1. 1. Lu t ency retuxafl,on
The amplitude of the early fall in tension, and the duration of the period
in which the tensio» is below its I csti»g vahic,;(I c h(lt fi f (»llul to il l ci «as(l
as the l r i uscfc iH str«t«fio(f (( SAN»(>w, l 04 4 ; A il »( ) ' I'T I i l i d J C ( T ( ' l i f z ,
1 061a). A . V . H i r . z ( 1 05 1b) has pointed o ii t t ha t t f i i s i s d i tFfc(lit t o
explain if.'it is assuuied tllat the rclaxatiou is (filo t (l; I, J(iugttlem»g o f ; i ,
Hlrl'll( lrlll'(I W fll(ill I H » l H( I' l(IH Wllrfl 'I II(3 (3'(l»Irl'll( lrlf (3 ( l(I»l(III I I( I ( (f W l l fl I f l (
" series clastic elcuieut" w h ich liuiit s th e r at e of r ise of t efisiou :
increase in the amplitude of the 1atency relaxatio» werc flue tn increase(l
stiA'riess of tlio series cfasti(: co»lpn»(;»t, 1 li«ii tile «it(l of I iso (lf'l o » H'I(>ti
ought to be iu c rcascd for t hc s auic reason, aud the t i me at w h i c h t ,fie
tension curvere-crossed the baseline ought to have been unchanged.
The observation would however be easily explained if the relaxation
was due to the lengthening of a structure in parallel with b oth th e con-
tractile and the series elastic elements. This was diKcult to fit in with
the accepted idea that the contractile material was continuous along
300
(iririf Z a p l ' i Ir'rNOM lrlirf A I N M fl H u f r z r
the fibre even at rest; ahuost thc ouly remaining possibility was the
th r improbable one thatthe latency relaxation took place in the
sarcolemma and did not involve the contractile material at all. e
d ifficulty disappears however if the sliding model is adopted. I f i t i s
supposed that some part of the resting tension is taken by the actin
filaments and the S f i laments by w hich they are joined, then the
latency relaxation could be the result of a lengthening of the actin
fil e n t s (Fig. 1) which could allow the elastic S filaments to shorten,
reducing their tension. If the tension in the S filaments behaves at a
like the total resting tension (increasing roughly exponentially with
stretch),the tension drop for a given elongation of the actin fi laments
will increase with muscle length. The S filaments are not stretched by
the contractile process and. therefore have nothing to do with the series
clastic element; there is therefore no reason to suppose that the latter
becomes less compliant with increase of muscle length.
On thisargument, the latency relaxation should represent a length-
ening of the actin filaments. There is at present no evidence for an
elasticconnection from the end of each myosin fi lament to the adjacent
8 line, but equally there is nothing to exclude this possibility; i f such
;I, thing existed it would be possible for lengthening of the myosin
filaments to produce a drop in tension,and. the latency relaxation
might represent achange in them and not in the actin fi laments. In
either case, however, it is necessary to assume that the lengthening
l,akes place in one typo of filament independently of the other, and does
not involve for instance a relative force generated between the actin
and myosin filaments.
In the sequence of events which follow stimulation of a muscle, the
change which underliesthe latency relaxation must come earlierthan
the contraction itself. I t i s t herefore probably a link in the chain of
events which leads to activation of the contractile mechanism, and if
i l iH irulced a change in the actin filaments, it is nat ural t hat t h e str u c -
ti»e which conveys activation inwards from the membrane should be
1(lcated in the I bands, as appears to be the case (p. 275).
V. 1. 2. 1n(;ri~.s(:in IorN(uiiut riryi<lily
if the
&TEN-KNUDszN (1953) found that the torsional rigidity of an isolated
fibre ofthe frog begins to increase before the main rise of tension,
I(;(lolling a p'latcau at a bo »t o ne-third. the contraction t i me a nd m a i n -
taining this level until well into the relaxation phase. He very naturally
explained this early rise as being due to an increase in the number of
cross-links between longitudinal protein chains, but this introduces a
difFiculty if the myosin and actin are d,istributed in the way shown in
I('ig. 1. Cross-links would be expected to be formed only in the xone
of overlap,and the low rigidity of the I and II bands would prevent
301
 M [18(>li(1 8 ' ( ' ( ( i « ( ' ( ( ' i( (( . ( N J> i « J( (r'«> (( ( (i>S «> i, ««>NrPJQQ(>i(~I(
a ny large change from being detected at the tendon ends. With t h e
fibre at "equilibrium length", where the actin filaments of the two ends
o f each sarcomere are j ust i n c o n t act a t t h e m i d d l e o f t h e A b a n d ,
STEN-KNUDsEN found a 20-fold increase of torsional stifFness, whik' the
l argest efFect that c o uld be expected froln i n creased rigidity i n t l i e A
bands alone is a fourfold increase, since at this muscle length the I bAnd
forms about a qu arter of the sarcomere. I t i s d i % 0ult t o suggest what
tihe llAtiu>'0 of tihe change ll la y b c , 081>001>illy As tilicl'0 18 no cv i d cl>00 l(t
present whether i t a r i ses within t h e f i b r i ls, from connections between
the fibrils (e.g. the 8 m e m b r anes) or from Sarcoplasmic structures.
7««. l. 3. V'he "a/I>ha I>ro«:es~"'
BRowN (1034, 1936, 1941) Showed that t h e a p p l icatioii o f A 131'essui'0
of a few hundred atmospheres to a muscle during the early part of an
i sometric t w l t cl i w o ul d c a use An in crease ill t h e p es,k telisioli a il(i i l l
the rate of rise of tension, even though the pressure had been reducecl
to normal by a tenth of the contraction time. BRowN'8 suggestion
(1941), that the high pressure acts by favouring the alteration in chemi-
cal behaviour of the muscle that results from stimulation, appears tn
require that the degree of activation in H n,7,'s sense should be increasecl,
b ut t h i s a p p ears t o c o n fl ict w i t h t h e e v i d ence ( H I I .I., 10400; M A r .-
I'HERsoN and W I L K IE , 1 0 54) that a c t i v a t ion i s c o m p l ete even i n A ,
twitch at atmospheric pressure. A possible alternative explanation is
suggested by the sliding mechanisnl, together with BRowN's further
observation that t h e application of pressure later in a t w i t c h (0.g. >(ea>
the peak) causes a sadden, fall o f t e n sion (As well a s a n a « c«1«rate«l
decay if t h e p r e ssure i s m a i n t a ined) . T h i s s u g gests t ha t i n c r ease(l
pressure causes lengthening of either the actin or the myosin fil a ment
(or both); if this is so, then a high pressure at the time when links are
first being formed between the actin and. myosin filaments will cause
the filaments t o b e c om e l m i t e d w i t h a gr e a t e r clegcee of o v e r l al>,
A nd the release (>I' prcssure will act j u s t l i k o ; (, q((ick stret«li, wh icli i s
known to c ause an i n crease in th e t e nsion Subsequently (Ievelopc(l i»
tile twit cll by liclpiiig t(> strctcli tli(> sc ries clastic cl('i>i(>>if s(H ((.i., f 04! >«}.
(>>'. I. 4. li ' a> lip «le«:1<,<J,
i«. .of «,(:l«.ii,r«',6>',lily
A. V, I'I J I Ji ( l 0 >ffl> f!Jr> l b), Sli(>wc(1 f,liaf, if* a iu(is«i(; is sf,i(>(((l:(fc(l wliil«
it is b eing St i c t c he(l, a(> f»0(("„Lsc «>f' f(;»si«»> is «l«>f(>«f„if>f«> af a » » ( (.f>
s horter i n t e r va l a f t e r t h e S t i m u lu s t f>«(» (luriiig a t wi t c l i w i t l i o l i f
stretching. T h i s effect b egins At, About, the same t im e As the l at ency
relaxation, aud it i (as been gene(ally assn(ued tli >t l>«>tl(;((0 manifesta-
tions of t h e s am e u n d erlying p r o cess. T h i s d oes not filt i ( ( 7viti> thc
hypothesis developed earlier in this article, since the earliest connection
between the actin and myosin filaments would generate tension; And
3(12
> O T(I 7: R ( ' 7 ( l i N O ME N A I N N U S CL l i
no change involving one type of filament only should be able to alter
the extensibility of the muscle; it also does not fit with the idea that
the latency relaxation is due to lengthening of filaments without
i nteraction between the tw o t y pes (p. 301). A n a l t ernative is t o
suppose that the tension-generating process (formation of links between
actin and. myosin) begins at a v ery lo w r at e early in t h e l atency
mlaxation. The amount of tension developed would at first be masked
by the relaxation, which is occurring in parallel at the same time, but
when the muscle is stretched, the decreased. extensibility due to the
links might cause the total tension to rise instead. of fall, T hat such
an overlap is possible is shown by SxNDow'8 (194'7) analysis of the time
course of the early tension changes, in which the rate of rise of the
component of tension generated by the contractile process itself was
taken to be proportional to the extent of the lengthening which
produces thelatency relaxation, and a very good.fit was obtained with
the overall tension change.
7>r. 1. 5. Ea r ly heat liberat(on
A . V. H I L I(1949a) has suggested that the heat liberated in a twitch
consistsonly of activation heat and shortening heat, there being no
component equivalentto the maintenance heat of a tetanus, which e
regards as composed of the summed elements of activation heat that are
liberated in response to the successive stimuli in maintaining the -
state
of activation. I n a sense, the scheme put forward. here (pp.. 279-284))
fits in with this, in that both activation and maintenance heat must
arise at least in pA,rt from th e Same reactions, but as far as t hat g oes,
shortening heat also arises from the same reactions. I t w o uld seem
>nore natural, if that scheme is correct, to regard. maintenance heat as
Something distinct from activation heat both in a twitch and. in a teta-
nus, the activation component being associated. only with the initial
decrease in the number of sites blocked by combination with XP (p. 283).
'I.'lie (atc ot' liberation o f a c t i v a t ion h eat w o ul d t h e n b e p r o p or t i onal
to the rate at which sites are being converted to the state in which the
linksbetween actin and, myosin can be formed.. The actual formation
«f' fli c links is fulther delayed because it takes place with a finite rate
constaut (f,p.281), so that the degree of activation, in the sense of the
ability to hold tension, which must be proportional to the nernher of
links in existence, lags by two steps behind. the rate of liberation of
;>ctivatioll heat . O n t l i i s basis, the early m a x i mu m i n t h e heat r at e i s
not direct evidence that activation is complete very soon after She
stimulus. The activationheat may also contain a component corres-
pond'ing ot t h e formation of the links between actin and myosin, but
reciably
thiscomponent could not, on this formulation, contribute apprecia
to the early peak.
 M 11S(11«1«1 8'I' IL I> ( 'I'1>1( l«l A N » ' I ' l l I«'(> IL I I«1 i (> V (,'(>N 'I' IL«L O'I' i» N
V. 1. 6. General discnssion of ectlychanf/es
The discussion in the last few sections has led to postulating three steps
in the activation process, apart,from membrane changes and the
i nward s p read a l on g t h e 7~ m e i n br anes. T h e s e st eps, w h ic h a g r ee
r ather closely w i t h t h o s e p o stulated b y S A N no w ( 1 9 47) i n o r d e r t o
account for th e early t ension changes, are:
(1) Some changes which allows the r( i actioii A X P --> A t- X + PO 4
to takeplace (reaction 3, p. 288).
(2) The reaction AX I ' ~ A + X + PO4 itself ; t h i s r e a c t io » i s
accompanied b y t he l i b e r a t io n o f " ac t i v a t i on. h eat " a n d b y t h e
lengthening whose early stages show up as the latency relaxation .
(3) The formation of the links between actin and inyosin by which
tension or shortening is generated. The "alpha process" would corresponcl
probably only to the earlier part of t his step: a s more links are formed,
a n increase of pressure would b e p r o gressively loss able to c ause the
r elative m o t io n b e t w een t h e t w o s et s o f f i l a m ents o n w h i c h i t w a s
assumed. (p. 302) that the effect depends. The increase of torsional
rigidity would presumably also correspond to this step.
S tep (1} m us t p r o ceed w it h a t i m e c o n stant o f o n e o r t w o m i l l i -
seconds in frog muscle at O'C, since thc rate of step (2), Ls I»(lic(Lto<t by
heat production, reaches its maximum in a time of this order (Hn,i„
19494, 1963a).
The time constant of step (2) might bo sot equal to t hat of t )io early
fall in the heat rate (after shortening heat has been deducted); from
A. V. HDL,'s work (1949O) this appears:to be roughly 25 insec. This
m ay well b e a n o v e restimate since th e a c t i v at ion h eat m a y c o n t a i n
an element corresponding to stop (8).
According to th e hypothesis developed on pp. 281 — 288, the rate
constant for stop (8) is (f - ~-r/). T)Iis v;L<i(:s;Lcc(>rding to thc relntiv(<
p ositions of t h e r e act ive sites ; a » a v e r age VL(iio for f/ wa s t a lo;» oii
p. 296 IL>I 0'7 soc" , ILIid (J - ~ - f/)/f/ was g i v ol i l «llo v«LI<io«J'88, s(> tll«Ll
(f + (/) would b e 8 6 0 sec ' , c o r r esponding t o a t i m e c o n st<L»t of
28 iiisoc.
Tl>OH(> l,iiii(> (;(>i>sl„»ilH I » > ; < l(«l»I (") I»i(l (8) Iir(' ; i l » ><il, i Ig>)it 1 (> IL(;(:(>ii»l
f or th o r i s e oi ' t u i s i o»a) i i g i d it y ( a ss»»iod t o c o r r espoiul t o s t o p 8 )
bohlg (',»lrliiloto :Ll I l l»>«I, l()0 »is(;(,:LI't( i' l li(; if,ii»I<I<is (;LII ti»1(;s 1(.f'(ii
to frog musclesat O'C).
V. 2. Decreased exfractabilLty foproteins
It has bee» known for a loiig tii»e that the fibrillar l» otei»s of muscle are
much moro easily got i»to solutio» fru»i fresh musclo th(LIL from muscle
in fatigue or rigor (Deuticke-Kamp e6'ect). At t h e same time a new
component appears in the extracts (contractine, DvzmssoN, 1950).
804
O Ti i E I L P H E N O M E N A I N MU ROI « E
BANGA and SzENT-GYQRGYI (1943} showed. that the decrease of extrac-
tability is largely explained by the union of actin and myosin, supposed
t,o be separate in the resting 6bre, to form actomyosin, but the observa-
tions of H A s sznEAcH (1S68) suggest that other factors may also be
involved. He found that a solution of ionic strength 0 0, containing
pyrophosphate, will extract the inyosin from minced muscle, leaving
6laments presumably of actin but removing the 8 lines. If the residues
are broken up with a blender i» the same solution, the actin is dissolved
as well (H Asszr,EAcH and >SGHNzmzz, 1951 ); similarly, this solution
dissolves both the actin and. the myosin from 6brils prepared from
fresh muscle (PEEEY, 1965). On the other hand, fibrils prepared from
inuscle in rigor mortis lose only their myosin on extraction with this
solution (HAsszLEAcH, 1S63), the actin filaments and the 8 lines being
retained.; fibrils from glycerol-extracted muscle appear to behave in
lho same way (HANsoN and H. E. HUxr.zY, 1953). Thus, both the 8
) ines and. the actin filaments are protected. by rigor from being dissolved,
while the actin 61aments, but not the 8 lines, are preserved in muscles
wliich has been minced but not broken up into fibrils. Clearly some
change has taken place in the material of the 8 line on rigor. Possibly
tl»s isenough to explain also the increased resistance to extraction of
t he actin f i l aments, or a n a l t e r at ion m a y h a v e t a k en. place in t h e m
too, which is an interesting possibility in connection with an earlier
suggestion that the actin 61aments may undergo a lengthening when the
inuscle is activated (p. 301).
T he existence of a change in the physical properties of the 8 l i n e
material further suggests that changes in t hi s structure may con-
ceivably be involved insome of the mechanical accompaniments of
activation (e.g. the increase in torsional rigidity). On the other hand,
i t also suggests that rigor mortis involves definite activation of t he
contractile substance (since the function of the 8 line appears to be to
tra»smit activation) a»d not merely a union between actin and m y osin
rosiilting d i rectly f r o m t h o r e d uced AT P c o n centration . S u g gestions
tliat, activation occurs in other kinds of rigor have recently been put
l '(»'w>Lr(l on ot her g r o u n ds ( SANI>ow IL»d > )GFINRYEIL (1965) for i o d o -
;L(;(;t;Llo rigor, a»d .I1AILNILN, Difzv aiul T i f @zt,l>Ar,i. (1966) for dinitro-
1>lie<i ol cont ractures).
V. 3. Op ILcal cILan//esAdoring
( a fwL/ch
V, 3. 1. ScatterLnf/of light
The early decrease in the amount of light di6racted by the striations,
discovered. by D. K. HD.i. (194S), was mentioned on p. 300. This early
change issoon masked by a much larger OKect, which appears to be a
decrease in the amount of light scattered by the muscle, and which
805

follows roughly the tiinc course of tiie tensioii (H<'IiAEincR and Copi<ERT,
1937; D. K . H l ' r L , 1040, 1053). T h i s scattering occurs almost entirely
in the direction at r i ght an gles to the long axis of the fibres, and must
t herefore be d u e t o l o n g i t u d i na l e l ements o f t h e m u s cl e s t r u c t u r e.
These are presumably (a) the outlines of the fibres themselves, and (6)
t he threads of sarcoplasm that li e between the groups of fibrils. If we
set aside the possibility that the change depends on an alteration in
the shape of thefibrcs, then the decrease is> scattering is probably due
to a decrease in the difFerence of refractive index between sarcoplas»i
a nd fibrils . I n i s o l ated fi bres under th e i n t erference microscope, it i s
quite clear that t h e sarcoplasm has a higher refractive index th an a ny
part of th e fi b r il s (A . I<. HiTxLzv a nd. NrEDERGERKE, 1054 ), so that a
decrease i n t h e r e f r a c ti ve i n d e x d i f fe r e nce c ould i n d i c a te e i t h er a
transfer of dissolved substances from sarcoplasm to fibr i ls, or of w at er
in the opposite direction; the second seems a more likely possibility.
There is no basis at present for estimating tlie magnitude of the shift.
V; 8, 2. Decrease fobirefringence
It is well established that the strength of the birefringence of striated
muscle falls during an. isometric t w i t cl i ( v o N MU RAI.'r, i<832; i ) u z i . I.>t
and COTTRELL, 1087 ), the amount of t h e fall being a maxi niu m ( a bout
30 per cent) if. the muscle is near its natural length. This effect niight
also be accounted for by the shift of water from fibrils to sarcoplasi»
which was suggested in the last section as an explanatio» of the decrease
i n scattering. T h i s could act i n t w o w a y s : fi r s t , b y c o ncentrating t h e
material which lies between the filaments in the fibrils, so reducing the
refractive index difFerence which causes the form component of t he
birefringence, and second, by reducing any contribution, analogous to
form birefringence, which may be made directly by the refractive index
< lifference between the threads of sarcoplasm and the fibrils. I f t h e
»Iovement ofwater.went so far that thc refractive i»<lcx <liffcrciice w:Is
actually reversed in ei ther of t h ese cases, then thc f o r» i b i r cl'ringo>ice
would increase again (since its strength is roughly proportional to the
sill>It>'< of tlio r<',I'!'>I« tive i»<1<!x <lifl'<!rci>« ! ); l l>i>> is <t 1><>s><
il>l< ! <!Nl>hw»ii I<»>
I<>I' l l><! <1<>l>l>l<>-I>>I
»>1><!<1 <'.III'v<t< I I» tl w<'!I'<! <>I>tel>l><!<I I>v v< >N M I > li s I 'I'.
'I'<AI»s<s(<»isi<»i
V. I.
V • 4 . 1 . Zl IJsOl'Ill <!'I'<< >i<'
l s
The absolute values for the tetanus tension pei unit cross-sectional
area that are t o b c f o und i n t h e l i t e r at ure for v e r t ebrate muscle vary
over a wide range. I<"rog muscle at O'C appears to give from 1 5 to
2kg/cm' (H I L L, 10 88; H A z D U, 1 051); a t r o o m t e m p erature, HA y DU
finds 2 5 kg/cms, while RAMszv and STREET (1040) obtained 3 5 kg/cms
8n6
<>'I'll ><lit 1'll It'N<>M I<N A l N M IISOI'il'I
from isolated fibres,which would correspond to about 3 kg /cms in.
whole muscle when allowance is made for intercellular space. Larger
values aregenerally quoted for mammalian muscle (e.g.5 kg/cms for
rabbit m u scle, WERER, 1055, p. 278 ) but RIToarz (1954) found only
1 5 kg/cms in rat diaphragm strips at 87'C. I t w o uld be valuable to
l.now whether these differences are real, or whether they are the result
oi' some accidental difference in technique or in the arrangement of the
i ibres; i f ' t hey ar e r eal, th e q uestion arises whether it i s t h e n u m b e r
of active sites that varies, or the tension developed. per site: the tension
lrig. 12. Arrangement of fibres in a muscle which might give a spuriously high
value for the tension pcr unit area. Tendon, black; muscle fibres, shaded. The
tension exerted at the tendons by the fibres shown is four times the tension
generated by any one Qbre, whilethe cross-sectional area of muscle fibre at
any point is only twice that of the oylindrical part of a single fibre.
per site is clearly i mportant i n d eveloping theories of contraction
(cf.p. 206). A point which does not appear to have been checked in all
c ases is whether the f i bres of th e m u scle run f ro m en d t o e nd . E v e n
if the fibres are parallel, it would be possible for an arrangement such
as is shown in Fig. 12 to produce a larger tension per unit area of the
whole muscle than exists within th e fi bres themselves. The great
majority of the fibres of the frog sartorius certainly run from end to
e»d, but it is well known that in the longer muscles of vertebrates, a
large number of fibres terminate with pointed ends within the muscle
(ROLLETT ) 18M; K R A USE> 1869, pp. 2 — 6; ADRIAN> 1925).
A. I<'. HUx Lz r a n d N z z DEROERKE( 1954) pointed out that, if t h e
tension in each filament is the sum of efFects generated at a number of
points ineach zone of overlap between actin and myosin, then, other
tliiiigs being e qual, a f i b r e w i t h b r o a d s a r comeres, and t h e r efore a
longer zone ofoverlap, would be expected to produce more tension
t lia<I one w it h n a r r o w s a r comeres. T h i s w o u l d b e c o m p ensated b y '
sl»w<;I contraciio», s i rico th e n u m be r o f c o n t r a ct in g z o nes i n s e r ies
(<l<>Ill>I<i the nuinbcr o f s a r coineres) wouhl be reduceil inproportion.
1 Asi'I.'It a»d PzzARD (1034) showed, in a comparison between different
I»<>soles of the same anima1 (eral>s and lobsters), that speed goes with
»Itrrowiiess of stri a t i on , an d 11>tzzzzR (1939) showed the same in a
comparison between the three pairs of legs of Dytiscus, but I do not
know of any data on absolute tension in these or similar cases. There
is no comparable variation be tween different st r iated m uscles of
vertebrates; the striation spacing at rest length appears to be remark-
ably uniform atabout 2 5 p.
807
 8'I'II I(( " I ' I ' I i z h N » 'I ' l l I <(> I(l ' I' e ( I I ' (' ( ) N ' ( ' I ' <((" I ' 1 ( I N
fllL
1h(ero dues not see»i to bo any oxplanatio(I al l>IT>sent for. t lie v;Lri(L-
tion of tetanic tension wit h t e m p erature, nor for th e f ailure of t ension
to be m ai nt ained i n a c o n s t ant c u r r ent c o n t r a ct ure.
V. 4. 2. Th e li m it to shortening in <L tet<inus
The fall of active t ension in a t e t a nus as a muscle is extended beyond
itsunloaded length finds a ready (though by no means proved) explana-
tion in the decrease of the width of eacli zone of overlap between actin
and myosin filaments, and. consequent decroase in the num ber of sites
at which tension can be developed (A. F . H v x L z v a n d à i z D z iLoziLKz,
1954; t h i s assumes that t h e sites produce tension in p a r allel). T h e> o
is no correspondingly simple explanation for the fall of tension with
s hortening below the unloaded length . T h i s t a kes the muscle into t h e
range of lengths where the actin filaments must be shortened (perhaps
crumpled at their ends); the force required to produce this deformation
might be directly reducing the tension which appears at the ends of
the muscle. In a tetanus which is not unduly prolonged, the extreme
shortening brings the muscle just about to the point where the myosin
filaments come into contact with the neighbouring Z lines; f u r ther
shortening only occurs (at any rate in frog muscle) if the muscle ie
brougl(t, into tl i o " d o l t a s t a t ( :" (14AMs>> .v and h T (LIizT, 1 9 40 ), which
involves irreversible changes in the muscle. Again, it is conceivable
that it is the stiffness of the myosin filaments that normally prevents
further shortening. A l t e r n a t i v ely, it m a y b e t hat t h o degree of activa-
tion is progressively reduced ae the muscle shortens; t h i s is suggested
by the experiment of KATz (1939, fig. 6) in which he allowed a tetanized
f rog sartorius t o s h o r ten c onsiderably an d d e v elop t ension ; h e t h e n
applied a load greater than it could. hold. but less than the isometric
tension the muscle could. produce at its rest length. This load stretched
the niusclo beyond the point where the isometric tension should have
b een enough to h ol d i t , a n d t h e m l i sclo thon shortene<l again t o t l i i s
p oint. T h i s e x p o r i m ont s u ggests t ha t t l i e d e g ree of a c t i v a t io n w e e
t emporarily r e d u ced, bu t t h e r e i s n o e v i d e nce w h et her t h i s w a e ( L
c(>(lso<1((clice ot t>llo eli(>l'loi((ilg as s l l c li, (>I' o'f 11((>I'ILl>I(1 el>i'ot(;li.
V. 5>. I>islr'<I>nfi oil o/' olh<!r s<L6sl«><«:>s
V. 5. 1. 8a rcopkmmic proteiris
lt w a s i i i o i i t / o tiod a i >ovo (p. 30(i) t>liat t l i o s(Lrcol>las(I1 llas (L higlioi'
r efractive index t h a n e ven t h e A b a n d s of t h e f i b r i ls, at an y r a t e i i i
isolated fiibres fi'oni tho frog. O n e w o uld n a t u r ally oxpe«t t lie reverse,
since rofractivo in(lcx ie probably a good measure of t h o t o t a l co(ice»-
tration of soM a n d d i ssolved mat ter p resent, and the fi br ils contain a
large amount ofactin and myosin in the form of filaments which are
308
('ITIi Z Z i ' 1 1 1 ( N O M Z N A 1 N M V RC L Z
'Lbsentfrom the sarcoplasm. Tho I bands probably contain some other
material as well as actin, since the refractive index difference between
A and I suggests that the total concentration in I is about P that in A
(A. F. H v x r ,zv an d N rz DzILozzKz, unpublished), while this ratio
should beabout < ifthe I bands oontained only actin.
Presumably either the filaments are very highly hydrated, or else
t,he soluble proteins of the sarcoplasm are at least partially excluded
f'Iom the spaces between the filaments. T h e second of t h ese explana-
tions is suggested by the observation of %z iizz (1934) that a dried
"myosin" thread placedin a 15 per cent myogen solution would take
»p fiivoor moro times its volume of water without any change of dry
weight,i.e.none of the myogen entered the thread. To explain this,
Wzl>zR postulated that the micellescomposing the thread must be
small enough,and.therefore numerous enough, to leave spaces no larger
than 90 A (based on a molecularweight of 81,000 for the main com-
ponent ofthe myogen, with an allowance for a shell of bound. water).
On a simple caloulation, the spaces between the filaments of fresh
muscle come out to be much larger than this. In t h e A b and, where
b oth sets of filaments are present, the X-ray data of H. E . H v x L z v
(1952; HANSONand H. E. Hvx Lzv, 1955) give the distance between
contres ofa myosin filament an'd each of its neighbouring actin fl la-
ments as 250 A; under the electron microscope the diameters of these
filaments are 110 and 40A r espectively (H. E . H v x r .zr , 1953a)„so
that thegap is 175 A. For this fi gure to be reduced to 90 A by hydra-
tion, the filaments would need. to be increased. to more than twice the
diameter found with the electron microscope, and even then the situa-
tion wouldnot be explained since the gape are very much wider in the II
region and inthe I band, and they also increase when the muscle is
allowed to shorten; also,such a degree of hydration would probably
be too highto be consistent with the strength of the form component
of the birefringence, unless perhaps the filaments are tubular as is
suggested. in some electron microscope photographs (H. E. H U E ,zV,
1953a; H ODGz, 1955 ). An alternative possibility is of course that the
librileare separated from the sarcoplasm by a membrane which is
i»(1>orinoablo to tho soluble proteins, but no such structure has yet been .
I i:1>ortod from oloctron microscope obeorvations; o r a g ain, " l o ng-r i n g e
1'orcce" may bo involved. T h o situation is altogether puzzling and
(lesorves further investigation.
V. 5. 2. Ul t r a -(>iolet absorbing riiciteri<il
The well-known measurements of CAspzzesoN and TaozzLL (1942)
show nearly all of the material with an absorption spectrum resembling
that ofthe purines to be localized in the I bands. They state (without
evidence) that 95 per cent of the material with this absorption consists
309

of the adenosine phosphates; if this ia correct, tlieir observations must
mean that the concentration of ATP in free solution in the muscle 6bre
is very much less than the average c oncentration obtained by d i v i d i n g
the fibre volume into the t otal amount of AT P p r esent. T h i s is clearly
a point o f g r eat i m p o r t a nce for i n t e r preting t h e r ole of A T P i n c o n -
t raction ; i t a p p e ar s t o b e c o m m o nl y a s s»Died t ha t a l l t l i o A T P i s
present in free solution.
There seem to be two loopholes i» CASPERssoN and Ti«)RELI.'s
work. Th e B rat is th at t h e ir m e asurements were made on fixed fibres,
and there waa no actual check that some ultra-violet absorbing material
did not escape from the fibres on fixation, though their photographs
certainly show t h a t t h e a p p earance of t h e f i b res was not n o t i ceably
c hanged. T h e s econd i a t h a t f i g u res fo r t h e n u c l eic acid c o ntent o f
muscle (DAvin soN, 1947; L z s L rz , 1955) suggest that AT P i » ay f orni a
much smaller proportion of the absorbing material than is assuined
b y CAsPERSsON and THoRELL. T h e l o c ation of t h e A T P i n t h e l i v i n g
6bre is of such theoretical importance that a check of these points
might be worth while.
It isinteresting that some of CAsPERssoN and THoRELL s photographs
show the ultra-violet absorbing band to be double, so that the distri-
buti(>>1 of absorbi»g n i a t orial (:or<'ospo»d>) tu t li o p o sition OI' tbe i V
bands, whichare probably formed by rows ofregularly aligned gran»les
(Itz'PE<US, 1890), togothor witli other sarcoplasmic structures.
CAsPERssoN and TH o R ELl' s expei'1111eiltial findinga wel'e conf<i'l»e(l
by KNasrzoM (1944), who also showed that the ash produced by
microincineration at 500'C waa localized in the l bands. He believed
this ash to consist of phoaphates, and to be derived from the adenylic
acidsand from creatinephosphate, but he did not mention as a possible
' source either the riucleic acids or the phoapholipids; the latter appear
to be concentrated inthe I band, at any rate in mammalian muscle
(DEMPszv et al., 1946).
I'l<)A(1 I A N I) i i>I I AN I< IL>1(1 lrh V I N ( I I)44) ILI>((>f()<lil(l iLba(>l'III II)ll ILI 2>5lI7 A,
agaul Iocaliaed in the I ba n d a ( H o AOLAND, 1946). T h e ir n l a t e rial waa
fixed in f o r m a li n an d s ectioiie<l iii p;LI;Lfii», but t l ) e re is no e v i <le»ce
Wll('!III('!I' H(>ll)(! I)f I II(! I)I I I'IL.V I(>l(!Ii ILI)s(>l' blllg lll)I
I ('I'I)ll III
L(I (!N(l>LI)('.ll.
VI . C ()N(a.<rsioNN
Aa a 1't'suit' ol ex po<'1)llelltILI wol'k wl licll IIIL>I I)(
!(!1), ()ILI'I'le(1 ollt lil t l ) e Iasl
three oi four y ears, it is at l ast possible to give interpretatio»s I'o> tlie
chieffeatures of the striations of nuiscle. The following points can be
regarded aa very w ell supported, though perhaps not established
beyond doubt in exactly the form stated.
(1) The A band does not change in width during stretch and moderate
shortening.
(! () N (! 1><I H 1 < )E I<
(2) The high refractive index and birefringence which distinguish
the A band aredue to rodleta of myosin.
(3) Filaments of actin run across the I bands and into the A bands
as far as the boundary of the less dense H region, which represents the
gap between adjacent seta of actin 6lamenta.
{4) Except in extreme shortening, changes of muscle length take
place not by stretching or shortening of either of these seta of filamenta,
but by their sliding past one another in each xone where they overlap.
(5) The dense Z line which biseots the I ba n d. is concerned with
conveying theinfiuence of the electrical changes in the 6bre membrane
which accompany excitation to activate the contractile myofibrils.
The point mentioned under{1)waa foreshadowed by much evidenoe
from nineteenth-century work, while evidence for (2) continued to accu-
mulate up toabout 1940. In each case, the old (and it now appears
inore correct ) opinion was generally discarded, on evidence which now
seems inadequate but which was supported at the time by theoretical
considerations. This re-emphasize the necessity for keeping experi-
mental dataclearly in view, whatever ideas about the mechanism of
contraction may be current.
These interpretations of the striation pattern are of great interest
from the point of view of the nature of the contraction process. In the
first place, they are sufficiently definite and detailed. to play their part,
alongside the biochemical and biophysical information, in the formula-
tioii of hypotheses. In the second. place, they are not easily reconciled
with the current idea that contraction takes place by the folding of pro-
tein chains at a number of links in seriea; they therefore suggest new
interpretations both of the contraction process itself and of many other
phenomena in muscle. The greaterpart of this article is devoted to
exploring some of the possibilities that are opened up in t his way,
A suggested mechanism of contraction, formulated with reference to
t,heidea that shortening takes place by SMing, not folding, and to the
I I<aiix facts of the resp<maes of glycerinated fibre preparations to A T P ,
is worked out ni sufficient detail to show that it oan account fairly
woll for the mechanical and thermal behaviour of muscle. Neither this
I l()w('vo>', noi' tho oxplariationa that are tentati v ely pro posed for various
otl)erphenomena, are at present beyond the stage of acting as working
I > y la) thos()s.
Nole added in pr oof
The experiments on local activation of e tnmacls fibre, apparently through
the g membrane (pp. 24 — 26), have been extended since this article waa
written ( A . F . HU Z L E Y, Pt ' oc. P h p aiol. 8o c. 2 — 3 November, 1 9 56).
The chiefnew findings are:
1. In crab muscle, the sensitive region ia not opposite the 8 l i nes
but is near to each boundary between A and L % ' hen the membrane
311
 A 'I (t HC>iiti « ' I ' I I ( I ( rr (J I( I( 4 ijt I) '('I( t~()tr ( I( « <) (" ( ' < ) N 'I' I ( r ( ( " I ' I ( )
is depolarized over such a point, only the adjacent half-I-band (from
Z to A-l boundary) shortens.
2 . The experiments on f r o g m u scle werc repented under th e i n t e r -
ference microscope, when the Z l i n e is clearly seen. I t w a s c on6rmed
that th e sensitive r egion i s o p p osite th e Z l i i i e , an d t h e c o n t r a ction
always involved both h a l ves of the I ba n <i eqttally, oven when I, weak
contraction was evoked by placing one edge of the pipette over the Z line.
3, The extent of t h e i n w ard spread of th e contraction in f r og fi bres
was found to be graded according to the strength of the applied
p otential even w hen t h e f i br e as a w h o l e was able t o r e spond t o a n
ordinary s t i n i i i lu s w i t h a n a l l - o r -none t w i t c h an d p r o p agated acti on
potential.
4 . In f r o g f i b r es, th e r ensitiv it y t o d e p o larization does not e x t e nd
continuously along th e l in e of c o n t act b e tw'een the Z m e n i b r ane and
the sarcolemma, but i s r estricted t o sp ots whose separatio i i along t h e
perimeter ofthe fibre is of the order of 6 p.
Most of t h e c onclusions reached on pp . 2 7 - 8 1 are «trengthcne(l by
these results as far as th e stri ated m u scle of vertebrates is concerned,
but clearly some struct ure other t ha n t h e Z m e n i b r ane is in v olved in
a rthropods. I n t he l a t t e r c a se, t h e Z l i n e s i»ust h av e s o i»e Other
{ (lit(){rl()lr (ct. l>. 3()) » IL(rd ((i I s l l k c l y I I l)l I I I)(' Z l i l t ( ' « <) l v ( ' I'I (> »I
b I'{ a
m uscle perforni t h i s f u n c t i on , w h at<eyer it m a y b ( « ; t s w e l l ; i s h e i n g
I»yolv('.d iii t lie Iiiwat'(i spiyca(i ol act;ivat (()».
Ill"irtsarcNc)"'<
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Akyosi»f ><l<.ris I'Jt@y. Arch. yes. I'/rysiul. Q35, 20;> — "!C,'J.
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Yl. ' I'HK U H L O R ()1'I,AS'I" JCJ'AL".I'l()N: I ' H O T OL Y SIS Ol' W A T E JC . 323

Y I I. I I N I I ' I ( '.S ()lr ' I ' l l K ( ' H I . O ICOJ/I,AST R K A OT JON 320

Y I I I. ICLrA("I'J()>VS ()I' ( ' H 1.()IC()J'I.AS'I'S O'I'HK R ' J ' HA N P H O T O L Y S I S . 33 2

JX. I C L'LAT 1()iV O K ( ' H l . ( ) l ( ( ) l ' I . A S'I' O'I'ICUUTUICI4 'I'O A O T I V JT Y . :U 3

N. 'I'HK U H I . OJCOI.'I.AS'I' ICKA(."I'10 iV I N Vy P O . 334

X I. S l ' I : (."I'ICAI, ()1EAN(;KS I N O J",I,L SUSPENSIONS

! VI I. ( ' l i l t ! Vlf I.trt>IJVilrS('JCN('I' ( ) l r ( , ' H I .OJCOPHYI.I . I X I' I V y)

N I I I. SUJ(1>>>JAR Y 330

ICKJrEJCKNOKS

' I'I« f o l l o w i i i g ubbrev i u t i or>s l>us< )><»i> iii«rl it> tliis u r t i c h»

I'(lA, p l i ospliogly r c ri c r>«id; A ' I ' I ' , s<loi>osine ti i p h o spl>st<.;
l)f'N+, dipliospho-pyridirie niicleotide; T l ' N , t ri p h o spho-pyridino nu«leotid«;
I) I'Nfl , 'I'PNH , t.he corr i e»on<ling re<li«r;d foisns; D V J ' <linit r o -pl>enol;
Ir Il V, f lu< ir> ir«)rior> ii< I«>l i< I<i