@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@a@@@@@ @ @ @ REVIEW OF LITERATURE @ e @ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

SKELETAL MUSCLE

Composition of ske le ta l muscle:

About 75% of t he weight o f ske le ta l muscle i s water.

Proteins const i tute about 20% which include t he pro te in concerned

w i t h contract ion (cont rac t i le pro te ins = 1 2 % ) and stroma pro te ins

and the usual ce l l u l a r enzymes ( 8 % ) . Other constituents l i k e

glycogen, adenosine t r lphosphate (ATP), c reat ine phosphate (CrP)

account f o r t he remaining percentage o f t he ske le ta l muscle.

S tmc tu re of ske le ta l muscle:

The ske le ta l muscle i s made up o f many long cy l i nd r i ca l

muscle f i b r e s which a re grouped into bundles ca l led fasc icu i i .

Besides t he muscle f i b r e s t he re i s a good amount o f connective

tissue, endomysium which surrounds t he muscle f i b res ,

per imys ium which surrounds t he fascicul i and epimysium wh ich

surrounds t he whole muscle. The slow muscle l i k e soleus

contains more connective t issue than t he fast muscle, extensor

d ig i to rum longus (e.d.1.; Boreham et al , 1988 ) .

The muscle f i b r e consists o f r e l a t i v e l y large amounts o f

cytoplasm, m u l t i p l e nuclei i n t he pe r i phe ry o f t he cytoplasm,

bundles o f m y o f i b r i l s containing t he cont rac t i le proteins, m l t o -

chondr ia and extensive sarcoplasmic ret iculum. Glycogen i s

d i s t r i b u t e d i n smal l c lus ters between the m y o f i b r i l s and among

t he cont rac t i le proteins. Recently, it has been shown tha t t he

cytoplasm also contains intermediate f i laments ca l led desmin,

l y l ng pa ra l l e l t o t he myo f l b r i l s . The desmin f i laments p l a y

an important r o l e i n maintaining the re l a t i ve pos i t ions o f

m y o f l b r i l s and o ther organelles In t he cytoplasm and probab ly

t ransmi t cont rac t i le forces t o t he sarcolemma (Wi l l iams et a l ,

1989).

The cont rac t i le pro te ins a re t h i n and t h i c k f i laments.

Besldes, i n t he cytoplasm there a re "'2'' p ro te ins located on t he

myosin f i laments at regular in terva ls and t i t i n which are thought

t o be responsible f o r t he character is t ic e l as t i c i t y o f t he muscle

f i b res (Wil l iams et a l , 1989).

The t h i n f i lament i s made up o f act in fi lament, t ropo-

myosin and troponin. Each troponin molecule cont ro ls t he

pos i t ion o f a tropomyosin molecule. I n turn, t he pos i t ion o f

t he tropomyosin molecule determines t he a b i l i t y o f seven ac t i n

subunits t o b i n d t o t h i c k f i lament.

The t h i c k f i lament i s made up of myosin molecules. The

myosin molecule on i t s head region car r ies a binding s i t e f o r

act in and a s i t e w i t h myosin ATPase. The t h i n and t h i c k

fi laments a re arranged so t ha t t he muscle f i b r e shows al ternate

d a r k (A) and l i g h t ( I ) bands. I n transverse section, t he

f l laments a re arranged i n such a way t ha t each t h i c k f i lament

i s surrounded b y s i x t h i n fi laments, The t h i c k f i laments a re

h e l d I n pos i t ion i n t he M l i n e which b isects A bands and t h e

t h i n f i laments a re anchored In t he Z l i ne which b isects I bands.

The s t ruc ture between the two adjacent Z l ines I s ca l l ed as

sarcomere.

Mechanism of muscle contraction:

The Huxley ' s s l i d i ng theory and Huxiey I s modi f ied cross

b r i dge theory (1974) i s t he w ide l y accepted mechanism of muscle

contract ion. I n b r i e f , t he act ion potent ial spreads through the

T-tubule which i s the invagination o f sarcolemma into the i n te r i o r

o f t he muscle f l b r e . I n response to t he action potent ial , t h e

f la t tened sacs o f sarcoplasmic ret iculum, ca l led terminal

cisternae, release calcium in to t he sarcoplasm around the

myo f i b r 11s. The mechanism b y which t he action potent ial causes

calcium release f r m the sarcopiasmic ret iculum i s not c lear ,

The membrane of t he T-tubules and terminal c isternae a re

connected b y long ho l l ow t h i n f i laments ( feet ) wh ich p robab l y

form the l i n k between the act ion potent ial i n t he T tubules and

the calcium release (Schnieder and Chandler, 1 9 7 3 ; La1 et al ,

1 9 8 8 ) .

The released calcium, b inds t o troponin C and causes

t he tropomyosin t o move l a te ra l l y exposing t he ac t i ve s i tes in

t he t h l n fi lament f o r myosin head. The cross br idges between

t h i c k and t h i n fi laments, a re formed. The myosin head due

t o t he presence o f ATPase, ac t i ve l y hydro lyses ATP. The resu l -

t ing energy, ADP and inorganic phosphate are s tored in t he

myosin head (even during t he res t ing condit ion before t he muscle

gets ac t iva ted) . U t i l i s i ng t he stored energy, t h e cross b r i dges

undergo conformatlonal change which i s sa id t o produce the ac t ive

tenslon In t he muscle, and ADP and Inorganic phosphate a re released,

I f fu r ther ATP i s avai lable, i t combines w i t h act in-

myosin cross br idge, dissociates them and in t ha t process i t

gets hydro lysed. Thus again myosin head car r ies stored energy

and hyd ro l ysed products of ATP. I f ac t ive si tes on ac t in a re

s t i l l remaining exposed, myosin heads get attached to them

forming t he cross br idges t o repeat t he cycles. The cyc ies

are repeated many times producing sl id inginof the t h i n fi laments

towards t he centre o f the sarcomere. Thus i t i s obvious t ha t

ATP not only prov ides energy for s l id ing i n o f the t h i n f i laments

bu t also causes the dissociat ion o f act in - myos i n comp I ex

for t h e myosin head to repeat the cycle. The cyc les a re

repeated as long as the calcium In t he sarcoplasm remains

elevated exposing the ac t ive s i tes on ac t in t o myosin heads.

The muscle re laxat ion is caused when the sarcoplasmic

calcium i s lowered b y the calcium re-uptake b y calcium pump

In t he sarcoplasmic ret iculum. The resu l t ing low calcium i n

t he sarcoplasm causes t he calcium bound to t ropon in t o

dissociate. The t ropon ln wi thout calcium a l lows the tropomyosin

t o cover t he ac t i ve s i tes on t he ac t in f i lament and t he t h i c k

and t h i n f i laments re turn t o t h e i r res t ing state. It should be

noted t h a t t he calclum pump o f sarcoplasmlc ret iculum has

calcium-act ivated ATPase a c t i v i t y and thus when two molecules

o f calcium are sequestered one molecule of ATP i s u t i l i sed .

Energy aspects of muscle contract ion and relaxat ion:

I n the above descr ip t ion o f t he mechanism i t i s apparent

t ha t ATP is t he immediate and u l t imate source o f energy f o r

muscle contract ion as wel l as muscle re laxat ion. The ATP leve l

In a muscle i s qu ie t meagre and is about 3 ~ M l g r a m o f muscle

which i s a d e q u a t e t o supp ly energy f o r maximal contrac-

t ions o f about 3 s. But ATP leve l is maintained dur ing contrac-

t ion b y the constant resynthes is o f ATP b y creat ine phosphate

(CrP) and thus ATP i s ava i l ab le f o r maximum contract ions o f

about 9 s.

Add i t iona l shor t term stores o f ATP can be regenerated

through anaerobic glycogenolysis from the stored glycogen in

t he muscle w l t h t he product ion o f lactate. These react ions

proceed under anaerobic condit ions and such glycogenolys is can

supp ly energy f o r maximal muscle contract ions o f about 90 s.

The long term regeneration o f ATP depends on t he ox idat ion o f

carbohydrates and f a t t y acids.

Muscle flbro types:

Skeletal muscle f l b r e s can be general ly c l ass i f i ed into

slow and fast f l b r e s (Close, 1972; Edwards et al , 1980). They

a re also ca l l ed as t y p e I and t y p e I1 f ibres . Each and every

ske le ta l muscle contains bo th f i b r e types in d i f f e ren t p ropo r -

t lons. I n some ske le ta l muscles t ype I f l b r e s a re predominent

(e.g. soleus); i n o ther ske le ta l muscles t ype II f i b r e s a re

predominent (e.g. extensor d ig i to rum longus). Some other

ske le ta l muscles have almost equal propor t ions o f bo th t ypes

1e.g. diaphragm). Again i n any given muscle, there i s trans-

formation o f one t y p e f i b r e into another as i t happens during,

development (Bu l l e r e t a l , 1960a; Close, 1964; Close, 1972).

exerc ise (K l rchberger and Schwartz, 19851, re innervat ion (Bu l l e r

e t a l , 1960b). exper imenta l ly a l t e red neural a c t i v i t y (Salmons

and Sreter, 1976), a l t e red pat tern o f d i r e c t muscle s t imula t ion

(Eken and Gundersen, 1988; Gorza et ai , 1988; Gundersen and

Eken, 1992). a l t e red t h y r o i d state (Izumo et a l , 1986; Caiozzo

e t ai, 1991; Calozzo e t a l , 1992) and a l t e red phys i ca l a c t i v i t y

(O i sh i et a l , 1992).

Type I f i b r e s contain numerous mitochondria, more c a p i l -

l a r i es around a f i b r e and more ox ida t i ve enzymes and have

slower cont rac t i le character is t lcs . Hence they a re we l l equipped

for aerob ic metabol ism and fat igue resistant. Type II f i b r e s

have fas ter con t rac t i l e character is t ics , fewer ox ida t i ve enzymes

and thus t hey a r e more su i ted f o r anaerobic metabolism (Essen

e t a1.1975). Type'il fibres)&nemoreATP,CrP and glycogenthan the t y p e I

f i b res (Soderlund et a!, 1992). The t y p e Ii f i b res are o f two

types. Type I IA f i b r e s have more o x i d a t i v e enzyme succinate

dehydrogenase (SDH) whereas t y p e 118 f i b r e s have less SDH

(Essen e t a l , 1975). Type I f i b r e s a re rec ru i t ed dur ing low

force vo luntary contract ions and t y p e II f i b r e s a re rec ru i t ed

dur ing h i g h force vo luntary contract ions (Col ln ick et al , 1974).

Type I f i b r e s have less myos in ATPase a c t i v i t y and t y p e I1

f i b r e s have more myosin ATPase a c t i v i t y (2.5 times as i n t ype

I f ib res ; Essen e t ai, 1975). Endurance t ra in ing increases t he

cross-sectional area o f t y p e I f i b r e s and s p r i n t o r strength

t ra in ing increases t he area o f t y p e II f i b r e s predominant ly

(Sa l t in e t al , 1976).

The p a m e t e r s of t h e con t rac t i l e fonctions:

The funct ions o f ske le ta l muscles a re t o produce tension

and to do work . Associated w i t h these functions t he requ i red

character is t ics o f t he ske le ta l muscles a re speed o f contract ion

and re laxat ion, s t rength ( f o r ce ) o f contract ion and endurance.

The speed o f shortening :

Th i s aspect I s usua l ly s tud ied b y t he t ime to reach t he

peak t w l t c h tenslon [Lewls et el, 1986; Russell et a l , 1984 ) .

T h i s t ime I s r e f e r r e d t o as contrsct lon t lme (CT). Close ( 1972 )

i n h l s r ev lew observed tha t t h e speed o f isometr ic t w i t c h

contract ion i s d l r e c t l y r e l a ted t o t he ra te o f h y d r o l y s i s o f ATP

b y myosin and thus myosin ATPase i s t he ra te l im i t l ng en- in

t he shorten ing process.

The speed of re laxat ion:

The re laxat ion ro te I s usua l ly i t u d l e d e i t he r b y assessing

the r a t e o f re laxat lon a f t e r a t w i t c h o r a f t e r a b r i e f tetanic

contract ion. Af ter a tw i tch , t he t ime taken to re lax upto 50%

o f t h e peak t w i t c h tension is measured (Lewis e t a l , 1986 ;

Nlsh io and Jeejeebhoy, 1991; Russell et al, 19841 and is known

as h a l f re laxat ion t ime ( 4 RT). Af ter a b r i e f tetanus t he

maximum dec l ine In tension i n 10 ms i s measured and expressed

as t he percentage o f t he peak te tan ic tension and t h i s r a te of

dec l ine of fo rce i s r e fe r red as maximum re laxat ion r a t e (MRR)

( B r w g h et al, 1986; Russell et al , 1984; Wiles et al, 1979 ) .

The speed of re laxat ion i s determined b y myosin ATPase

a c t i v i t y . Studies o f s ingle motor un i ts showed tha t un i ts w i t h

fast contract lon and re laxat ion t imes had h ighe r myosin ATPase

a c t i v i t i e s than slow un i ts (Burke et al , 1973 ) . Thus. t he re laxa-

t l on ra te o f t y p e II f i b res i s about two t imes that o f t ype I

f i b r e s (Wiles e t al , 1979 ) .

The re laxat lon ra te i s also influenced b y the energy

ava i lab le f o r pumping o f calcium in to sarcoplasmic ret iculum and

It was rhown t o be l i nea r l y re la ted t o t he ATP f ree energy

change i n t he ske le ta l muscle [Dawson et a l , 1980; P icha rd

e t a i , 1988).

Fina l ly , t he re laxat ion ra te also may be re la ted to a l te ra-

t ions I n t he number o f ca2+ adenosine t r iphosphatase molecule

i n t he sarcoplasmlc ret lculum and thus a reduct ion in calcium

adenosine t r lphosphate a c t i v i t y would decrease the ra te of re laxa-

t l on (N lsh io and Jeejeebhoy, 1991) .

Strength ( force) o f contract ion:

The strength o f contract ion o f t he skeletal muscle is

modulated b y t he number of motor un i ts r ec ru i t ed and t h e

frequency o f act ion potent ia ls i n t he motor un i ts . The to ta l

tension also depends on t he number of muscle f i b r e s in t he

muscle and the number o f myofilarnents p e r f i b re . At optimum

length o f t he ske le ta l muscle t he maximum isometr ic tension i s

about 2-3 kglcmz cross sectional area I n soleus and e.d.1. o f

r a t s and It i s sa id t ha t there i s no marked d i f fe rence i n t he

i n t r i ns i c strength o f t he cont rac t i le mater ia l o f fas t and slow

muscles (Barany and Close, 1971 ; Close, 1969) . Arrangement

of t h e f i b r e s w l t h i n a muscle determines t he number o f f i b r e s

which can be present i n t he musc leandthereby the tension

produced b y it. A muscle whose f ibres are arranged pennately

contains greater number of f l b res and thus can produce more

tenslon than a muscle of s imi lar size w i th f ibres arranged in

a para l le l fashion (Poland et e l , 1977) . Usually, the strength

I s measured as the peak tw i t ch tension or peak tetanic tension

b y stlmulating the motor nerve at various frequencies wi th supra-

maximal stimul I.

Endurance:

This aspect o f muscle function measures how long the

muacler can continue in t h e i r ac t i v i t y . This is measured as

the t ime upto which 50% of peak tetanic tension is maintained

(endurance time; E T ) , I t i s also measured as the percentage

decrease in tenslon from the maximum tetanic tension in a

specif ied time (fatigue index; Mandal et al, 1 9 8 9 ) .

Endurance exercise o f h igh intensity depends to a great

extent on the nu t r i t i ve support o f the muscle especially on i t s

stored glycogen content. Thus endurance i s greatly enhanced

b y a h igh carbohydrate d iet than b y a mixed d ie t or h igh fat

d ie t (Hultman, 1989) . Carbohydrate d ie t causes a glycogen

storage of - 40 glkg, a mixed d ie t 4 2 0 glkg and a h igh fat

d ie t e 6 g l k g muscle (Cuyton, 1 9 9 1 ) . Among the fast and slow

muscle f lbres, the slow f ibres are better equipped for greater

endurance due to greater myoglobin content, greater number of

mltochondrla, greater c a p i l l a r y / f i b r e r a t i o and greater res t ing

as we l l as maximum b lood f low as compared t o t he fas t f i b res .

For endurance exerc ise o f low in tens i ty but o f long dura t ion f a t t y

acids IFFA) d e r i v e d from adipose t issue and fran intramuscular

stores a re t he p r ima ry fuel (Hultman, 1989).

Effect of mdarnutrltion on ske le ta l muscle:

Undernut r l t lon dur lng t h e c r l t l c a l phases of g row th and

development i s known to have long term consequences. Skeletal

muscles, wh i ch const i tute major b u l k o f t he body, grow b y

hype r t rophy and nucleus mu l t i p l i ca t i on in t he postnatal pe r i od

(Enesco ad Puckty (1964); Wil l iams et al , 1989). Insuff ic ient d i e t a r y

intake causes wasting o f muscles. Undernut r i t ion dur ing t he

pe r i ods o f development causes permanent reduct ion i n DNA content

o f t he muscle. Coplnath et a l (1983) have shown t h a t t he

re ta rded g row th of ske le ta l muacle Is not recovered completely

b y rehab i l i t a t i on . I t i s a lso claimed tha t those who have

suf fered from undernut r i t ion i n t h e i r ch i l dhood often seem to

have reduced work ing capac i ty i n t h e l a te r years o f l i f e .

Structural changes in undernutr i t ion:

Undernut r i t ion i s known t o cause a t rophy o f t he muscle

f i b r e s thereby reducing t h e i r size. Type i I f i b res a re more

aff- than t y p e I f ib res . I n a state o f energy c r i i i s t he size

o f t y p e I f l b r e s i s be t t e r p rese rved than t y p e II f ib res . Th i s

may b e due to t he fact t ha t t he ac t iva t ion thresho ld o f t he

t y p e I f l b res I s lower as compared to t ype I1 f i b res and the

consequent increased chances o f ac t iva t ion may be decreasing t he

responsiveness t o starvat ion. Preservat ion o f t ype I f i b res seems

to be advantageous because the energy expenditure per un i t tension

developed b y type I f i b res i s lower than t ype II f ib res . Thus,

prerervat lon o f type I f l b res according to Henricksson (1990) i s

one of t he poss ib le mechanisms f o r economizing energy i n t he

energy def ic ient condit ion. During undernutr i t ion type II f i b res

are sa id t o become t ransfer red t o type I f i b res (Lewis et al,

1986).

Undernutr i t ion decreases t he amount o f connective tissue.

I n ra t s semistarved f o r 100 weeks t he connective t issue content

o f muscle i s approx imate ly 50% as compared to control r a t s

(Boreham e t a i , 1988 ) . Such decrement o f connective t issue in

undernutr i t ion might be benef ic ial because the increased leve ls

o f connective t issue i s often associated w i t h increase i n t he

pass ive resistance o r st i f fness o f t he muscles. Prolonged food

depr iva t ion (semistarvat ion) has no signi f icant ef fect on t he

muscle c a p i l l a r i t y as t he d ie t r es t r i c t ed ra t s show s im i l a r

c a p i l i a r y l f i b r e r a t i o when re la ted t o f i b r e size i n soleus and

e.d.1. as compared t o control r a t s (Boreham et al , 1988). Thus,

the major changes In undernourished muscles include t he trans-

formation o f t ype II f l b res t o t y p e I f i b res and decrement i n

connective tissue.

Blochemica! changes i n undernutr i t ion:

Undernut r i t ion I s known to cause degradat ion o f m y o f i b r i l -

l a r proteins. Brooks e t a l (1983) have shown tha t t he cont rac t i le

pro te ins decrease t o 65% of control leve l a f t e r 8 days o f s tarva-

tion. Lowel l et a l (1986) have noted t ha t dur ing b r i e f and

prolonged s tarvat ion m y o f l b r l i l a r pro teo lys is s t a r t s occurr ing

w l t h l n 24 hour8 o f 8tarvat lon I n pe r fu red r a t skeletal muscle.

S lm l l a r l y , Kadowakl et a l (1989) have shown tha t s tarvat ion f o r

3 days increases m y o f i b r i l l a r degradation p re fe ren t i a l l y than t he

nonmyo f l b r i l l a r pro te ins . I n t h i s connection, i t should be

mentioned tha t t he availability of l i p i d fuels has been shown

to cause pro te in sparing i n ske le ta l muscle dur ing prolonged s tarva-

t ion (Lowel l edC&an (1987). Emery et a1 (1986) also noted that

ske le ta l muscle p ro te in synthesis decreased progress ive ly dur ing

four days o f fast ing i n ra t s . L i a r lCo ldxrg (1976) have po in ted out

that b e n e r preservat ion o f pro te in synthesis occurs in slow tw i t ch

f i b res than t he fast t w i t c h f l b res .

Hypocalor ic feeding f o r 21 days has resu l ted i n a signi-

f icant reduct ion i n CrP and ATPlADP r a t i o and signi f icant increase

i n ADP l eve l i n t he gastrocnemius muscle o f r a t s (Russell et al ,

1984). i n t he above study muscle glycogen and ATP leve ls are

66% and 88% of t he control ra ts . Thus, biochemical ly, t he energy

substrate leve l and t he cont rac t i le pro te ins a re reduced due to

prolonged undernutr i t ion.

The a l t e red ske le ta l muscle funct ion in undernutr i t ion:

Undernut r i t ion resu l ts i n Impaired con t rac t i l i t y o f ske le ta l

muscles. A s ign i f icant reduct ion i n transdiaphragmatic pressure

at most o f t he st imulat ion frequencles and i n endurance capacity

were not iced I n t he s tarved ra t s (Dureu l l et at, 1989). These

authors explained t he observed changes In t he transdiaphragmatic

pressure i n terms o f t he reduct ion i n t he diaphragmatic weight

o f t he s tarved animals. S imi la r observat ions were made b y

Shlndoh e t a l (1991) i n diaphragm s t r i p s o f 3 days fasted

hamsters. However, Lewls ad Sie& (1990) have observed tha t nu t r i -

t ional dep r i va t i on f o r 3 days i n adu l t r a t s has not caused any

e f fec t on t he con t rac t i l i t y o f t he diaphragm s t r i p s and they noted

a signi f icant reduct ion i n fat igue index, s im i l a r propor t ion o f

t ype I and t y p e Ii f i b res and s im i l a r cross sectional areas o f

bo th f i b r e types i n t he nu t r i t i on dep r i ved diaphragm s t r i p s as

compared t o control . Lewis arl Sie& (1992) i n a subsequent study

I n adolescent r a t s observed tha t 90 h acute nut r i t iona l depr iva t ion

caused slowing o f t he contract ion and re laxat ion processes and

reduct ion i n t he diameter of t he diaphragm muscle f ib res .

The studies using l i m b muscles presented d i f fe rent resu l ts .

Russell et a l (1984) observed i n gastrocnemius muscle preparat ion

( i n s i t u ) that t he maximal fo rce was not reduced w h i l e t he

maximal re laxat ion r a t e and endurance were reduced i n 2 and 5

days fasted ra ts . I n addit ion, same authors also observed tha t

t he t e t rn l c fo rcer a t var ious ~ t l m u l a t l o n frequencies presented

s h i f t t o l e f t o f t he frequency-force curve.

N l h l o ad Jeej* (1991) using t he h i n d l i m b muscles soieus

(soleus) and extensor d ig i to rum longus (e.d.1.) w i t h two d i s t i nc t

f i b r e compositions (soleus: 85% t y p e I f i b res ; e.d.1.: 97% t y p e I1

f i b r e s ) demonstrated t ha t s lowing o f re laxat ion ra te occurred i n

bo th soleus and e.d.1. a f ter 1 week o f hypoca lor ic feeding bu t

not a f ter 2 days o f fasting. I n t he subsequent i n s i t u study

N l sh lo mdJeejePbhDy(l992balm po in ted out that 2 days o f fast ing had

l i t t l e e f fec t on t he o ther muscle cont rac t i le functions o f soleus

and e.d.1.

S imi la r ly , i n obese pat ients Russell et a1 (1983) have

observed tha t hypoca lor ic feeding f o r 2 weeks causes a s ign i -

f icant s lowing o f maximal ra laxat ion rate, a signi f icant increase

i n force o f contract ion a t 10 Hz and reduced endurance. Lopes

et a i (1982) have made s im i l a r observat ions i n pat ients w i t h

gastrointest inal d i so rde rs o f 1-6 months durat ion. Lopes et a l

(1982) and Russel l et ai (1983) demonstrated t ha t a l l the a l te red

muscle functions due t o undernut r i t ion were r e v e r s i b l e w i t h nu t r i -

t ional supplementation. Russel l et a l (1984) showed s im i l a r

resu l ts i n gastrocnemius muscle a f t e r 21 days o f hypoca lor ic

feeding (25% of food intake) in ra ts .

Kelsen e t a l (1985) using Isolated diaphragm s t r i p from

4 weeks underfed hamster ( feed was reduced b y 33% of control

food Intake) noted t h a t t he maximum isometr ic force was reduced

due t o reduct ion i n t h e mumcle mars and the cross sectional area

o f t he fast f l b r e s was reduced, as compared to control .

S iml la r observat ions were made b y Lewis et a1 (1986) who

demonstrated a s h i f t t o l e f t o f t he frequence-force curve and

Increased endurance t ime o f t he diaphragm s t r i p from 6 weeks

nu t r i t i ona l l y dep r i ved (feeding was 33% of cont ro l ) adu l t ra ts .

Most o f the studies mentioned above imposed undernutr i t ion

randomly i n t h e adu l t l i f e bu t not dur ing the pe r i od o f g row th

and development. Raju ( 1 9 7 4 ) in h i s study imposed nu t r i -

t lonal stress i n t he c r i t i c a l phases o f growth and development

pe r i od o f r a t s s tar t ing from b i r t h t o 13 weeks o f age and

concluded tha t t he extent o f recovery i n skeletal muscle

performance and metabolism was incomplete even a f t e r prolonged

rehab l i i t a t i on f o r 15-20 weeks. However, Raju ( 1 9 7 4 ) has

s tud ied only t he endurance aspect o f t he muscle function, i n t he

rehab i l i t a ted animals but not i n t he undernourished animals.

Thus, t he l i t e ra tu re suvvey c l ea r l y indicates t ha t there

i s pauc i ty o f study regarding t he skeletal muscle functions due

to undernut r i t ion dur ing the growth and development period.

i n addi t ion, we have not found any study re la t ing to t h e

consequences o f t h e combined ef fects o f undernutr i t ion and forced

phys ica l a c t i v i t y (exercise) imposed i n t h e growth per iod, on

skeletal muscle functions. Exerc ise i s known t o cause pro te in

spar ing and Czerwinski e t a l ( 1 9 8 9 ) have shown tha t in r a t s

regular endurance t ra in ing on t readmi l l prevents exper imental ly-

induced muscle atrophy, p robab ly b y reducing the breakdown o f

myosin heavy chain in the skeletal muscle. Sakamoto r n d G m w a l d (1987)

showed tha t addi t ions of t readmi l l exercise fo r 8 weeks in fast ing

ra ts o f 4 weeks age resul ted in improved growth o f the animals

as compared t o fast ing r a t s wi thout the t readmi l l exercise.

However, the consequence o f the combined effects o f under-

nu t r i t ion and phys ica l a c t i v i t y dur ing growth and development,

on muscle function has not rece lved suff ic ient attention.

SMOOTH MUSCLE

Structure:

Visceral smooth muscle i s composed of mononucleated

sp ind le shaped myocytes. The myocytes arranged w i t h t h e long

axes p a r a l l e l t o the d i rec t ion o f contraction, a re kept in small

bundles ( f a r c i c u l l ) w i t h the In te rce l lu la r connections o f gap junc-

tions and desmosomes between t h e myocytes. These bundles are

separated b y connective t issue. Fascicul i l i e in para l le l in the

muscular is externa o f the intestine. The myocytes contain, c losely

packed f i ne f i laments l y i ng pa ra l l e l to t he long ax is , golgi

complexes, mitochondria and endoplasmic ret iculum. An i r regu lar

and poo r l y developed sarcopiasm l c ret iculum ramifies between the

myof l laments and also l i e s beneath t he sarcolemma.

The myof l laments a re t h i c k and t h i n fi laments. Each t h i c k

f i lament I s surrounded b y about 1 5 t h i n fi laments. The t h i n

f i laments a re attached t o dense bodies some of wh ich a re

d ispersed w i t h i n t he c e l l and some are attached to t he c e l l

membrane. The dense bodies o f smooth muscle serve t he same

r o l e o f Z discs In t he ske le ta l muscle, namely anchoring t he ac t in

fi laments. Troponin is not present i n smooth muscle but it

contains calmodulin, another calcium regulat ing pro te in .

Tropomyosin is found i n vascular and v i sce ra l smooth muscles

occurr ing I n t he r a t i o 1 :50 ( tropomyosin:act in).

Mechanism of contrrtion and relaxation

The sequence o f events i n contract ion i s as fol lows:-

- Nerve st imulat ion, hormonal st imulat ion, s t re tch o f the

smooth n~usc le f i b r e . - Calclum ent ry b y a voltage-dependent inward current

mechanism. and lor

Calcium released from the sarcoplasmic ret iculum.

and 1 or

Calcium released from in t race l lu lar b ind ing si tes.

- Increase i n ln t race l lu lar calcium.

- Calcium ions b i n d w i t h calmodulin.

- Calcium-calmodulin complex act ivates myosin kinase.

- Act iva ted myos in kinase causes phosphory l a t ion o f

rcgu la tory chait i o f n ~ y o s l n head.

- The head a t ta ins t he a b i l i t y o f b ind ing w i t h t h i n f i lament.

- Sl id ing o f ac t i n and myo r l n f l lsments leading to muscle

contract ion.

The sequence of events i n re laxat ion i s as fol lows:-

- Sequestration o f calcium b y sarcoplasmic ret iculum.

and lor

Sequestration o f calcium b y in t race l lu lar b ind ing s i tes .

and 1 o r

Act ive (ATP requ i r ing) pumping out o f calcium.

- Lowered in t race l lu lar calcium leve l

- The steps invo lved In contract ion reverse.

- Myosin phosphatase gets act ivated.

- Dephosphoryiat ion o f regu la tory l i g h t chain.

- The contract ion stops, leading t o relaxat ion.

Energy aspect of contraction:

ATP I s t he major source f o r fo rce development. However,

t o maintain s im l l a r tension, smooth muscle uses h igh energy

phosphate much more s lowly [approx imate ly 200 t imes slower)

than s t r i a ted muscle. Hence, t he r a t i o o f t he energy requ i red

t o r u r t r l n a l m i l r r amount o f tenr ion b y smooth and ske le ta l

murc l ra i s 1 :200 ( r pp rox lma te l y ) .

F o m of m u r i a on traction:

In teres t ing ly , t he maximum tension developed b y smooth

muscle I s s l m i l a r t o t ha t o f ske le ta l and card iac muscle (Giles,

1983) . However, compared w i t h ske le ta l muscles, t he tenslon

development In smooth muscle i s ex t remely slow.

P a r m e t e r s of coat roc t i le functions:

Determination o f tension produced b y isolated segments

(Jayasundar and Vohra, 1977; Johnson et al , 1978; Saha et al ,

1992) , contract ion pressures b y t he isolated o r intact v iscera

(Maggi and Mel i , 1982; Meunier e t a l , 1978) and t r ans i t t ime

(Staniforth, 1989) a re t he usual parameters f o r studying t he

contract1 l e functions o f smooth muscle.

Effect of undernut r i t ion on smooth muscle:

Undernutr l t ion, as I n skeletal muscle, causes

tremendous reduction in t h e smooth muscle mass. For instance,

i n severe c h r w i c s tarvat ion t he wal l o f smal l intest ine i s so

much reduced tha t it I s almost transparent. During a study on

t he e f fec t o f four days fast ing i n ra t s there was an abrupt r i s e

In p ro te ln breakdown i n smooth muscle from the f i r s t day o f

fast ing (Emery e t al , 1986) . Thus, there was reduct ion i n t he

weight o f m a i l intest ine i n 3 days o f fast ing (Bu r r i n et al, 1988)

and t h e length o f small intest ine was also reduced b y four days

s tarvat ion (Goodlad et al , 19881. Funct ional ly, Tayo (1984) has

shown tha t fast ing f o r 1-3 days reduces t he cont rac t i le responses

o f smooth muscle of vas deferens.

Long term studies have shown more severe reduct ion in

smooth muscle mass. Firmanayah et al (1989 ) have shown that

i n 6 weeks o l d r a t s subjected t o prenatal fo l lowed b y postnatal

undernutr l t lon, t he re i s severe reduct ion in t he mass o f small

Intest ine and colon b y about 58% and in length o f these structures

b y about 23%, as compared t o those i n f ree fed ra ts . However,

i n prolonged undernut r i t ion there might be some adapt ive

mechanisms for maintaining t he functions of intestines.

Venkataraman et a l (1983 ) have shown tha t the response to

exogenous acetylchol ine i s 2-3 t imes increased in t he duodenum

o f 21 days semistarved adu l t r a t s .

Thus, t he l i t e ra tu re survey indicates that undernutr i t ion

produces reduct ion i n t he mass o f smooth muscle and increases

sens i t i v i t y t o t he t ransmi t ter acetylchol ine. It i s c lear from

the l i t e ra tu re survey that there i s a lack o f information on smooth

muscle functlon i n prolonged undernutr i t ion occurr ing throughout

t he growth and development phase o f t he ind iv idua l . Besides, there

I s also a pauc l ty of information regarding t he combined effects o f

undernut r i t lon and forced phys i ca l a c t i v i t y on smooth muscle function