Skeletal Muscle (Extra Reference)

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Skeletal Muscle Physiology



Muscular System Functions

• Body movement (Locomotion)

• Maintenance of posture

• Respiration

!iaphragm and intercostal contractions

• "ommunication (#er$al and Facial)

• "onstriction of organs and vessels Peristalsis of intestinal tract

#asoconstriction of $%v% and other structures (pupils)

• &eart $eat

• Production of $ody heat ('hermogenesis)



Properties of Muscle

• Excitability: capacity of muscle to respond

to a stimulus

• Contractility: a$ility of a muscle to shorten

and generate pulling force

• Extensibility: muscle can $e stretched $ack

to its original length

• Elasticity: a$ility of muscle to recoil to

original resting length after stretched



'ypes of Muscle

• Skeletal ttached to $ones

Makes up *+ of $ody ,eight

Responsi$le for locomotion- facial e.pressions- posture- respiratory movements-other types of $ody movement

#oluntary in action/ controlled $y somatic motor neurons

• Smooth

0n the ,alls of hollo, organs- $lood vessels- eye- glands- uterus- skin

Some functions1 propel urine- mi. food in digestive tract- dilating2constricting pupils- regulating $lood flo,-

0n some locations- autorhythmic

"ontrolled involuntarily $y endocrine and autonomic nervous systems

• Cardiac

&eart1 ma3or source of movement of $lood

utorhythmic

"ontrolled involuntarily $y endocrine and autonomic nervous systems



Connective Tissue Sheaths

• "onnective 'issue of a Muscle Epimysium% !ense regular c%t% surrounding entire muscle

• Separates muscle from surrounding tissues and organs

• "onnected to the deep fascia

Perimysium% "ollagen and elastic fi$ers surrounding a group ofmuscle fi$ers called a fascicle

• "ontains $%v and nerves

Endomysium% Loose connective tissue that surrounds individual

muscle fi$ers• lso contains $%v%- nerves- and satellite cells (em$ryonic stem cells

function in repair of muscle tissue

• "ollagen fi$ers of all 4 layers come together at each endof muscle to form a tendon or aponeurosis.



5erve and Blood #essel Supply

• Motor neurons

stimulate muscle fi$ers to contract

5euron a.ons $ranch so that each muscle fiber (muscle cell) is

innervated

Form a neuromuscular 3unction (6 myoneural 3unction)

• "apillary $eds surround muscle fi$ers

Muscles re7uire large amts of energy

8.tensive vascular net,ork delivers necessary o.ygen

and nutrients and carries a,ay meta$olic ,aste

produced $y muscle fi$ers



Muscle 'issue 'ypes



Skeletal Muscle

• Long cylindrical cells

• Many nuclei per cell

• Striated

• #oluntary

• Rapid contractions



Basic Features of a Skeletal Muscle

• Muscle attachments

Most skeletal muscles

run from one $one to

another

9ne $one ,ill move

other $one remains fi.ed• 9rigin less mova$le

attach: ment

• 0nsertion more

mova$le attach: ment



Basic Features of a Skeletal

Muscle• Muscle attachments (continued)

Muscles attach to origins and insertions $y

connective tissue• Fleshy attachments connective tissue fi$ers are

short

• 0ndirect attachments connective tissue forms atendon or aponeurosis

Bone markings present ,here tendons meet $ones

• 'u$ercles- trochanters- and crests



Skeletal Muscle Structure

• "omposed of muscle cells (fi$ers)-connective tissue- $lood vessels- nerves

• Fi$ers are long- cylindrical- and

multinucleated

• 'end to $e smaller diameter in small

muscles and larger in large muscles% ;mm: cm in length

• !evelop from myo$lasts/ num$ers

remain constant

• Striated appearance

• 5uclei are peripherally located



Muscle ttachments



ntagonistic Muscles



Microanatomy of Skeletal

Muscle



Muscle Fi$er natomy

• Sarcolemma : cell mem$rane

Surrounds the sarcoplasm (cytoplasm of fi$er)

• "ontains many of the same organelles seen in other cells

• n a$undance of the o.ygen:$inding protein myoglobin

Punctuated $y openings called the transverse tubules (T-tubules)

• 5arro, tu$es that e.tend into the sarcoplasm at right angles to thesurface

• Filled ,ith e.tracellular fluid

• Myofibrils :cylindrical structures ,ithin muscle fi$er

re $undles of protein filaments (6myofilaments)

• ',o types of myofilaments

– ctin filaments (thin filaments)

– Myosin filaments (thick filaments)

– t each end of the fi$er- myofi$rils are anchored to the inner surface ofthe sarcolemma

–

<hen myofi$ril shortens- muscle shortens (contracts)



Sarcoplasmic Reticulum (SR)

•SR is an ela$orate- smooth endoplasmic reticulum runs longitudinally and surrounds each myofi$ril

Form cham$ers called terminal cisternae on either sideof the ':tu$ules

• single ':tu$ule and the = terminal cisternae forma triad

• SR stores "a>> ,hen muscle not contracting <hen stimulated- calcium released into sarcoplasm

SR mem$rane has "a>> pumps that function to pump"a>> out of the sarcoplasm $ack into the SR aftercontraction



Sarcoplasmic Reticulum (SR)



Parts of a Muscle



Sarcomeres1 ?

!isk to ? !isk

• Sarcomere : repeating functional units of amyofi$ril

About 10,000 sarcomeres per myofibril, endto end

Each is about !m lon"

• !ifferences in si@e- density- and distri$utionof thick and thin filaments gives the musclefi$er a $anded or striated appearance%

$ands1 a dark $and/ full length of thick(myosin) filament

M line : protein to ,hich myosins attach

& @one : thick $ut 59 thin filaments 0 $ands1 a light $and/ from ? disks to ends of

thick filaments• 'hin $ut 59 thick filaments

• 8.tends from $and of one sarcomere to $and of the ne.t sarcomere

? disk1 filamentous net,ork of protein% Servesas attachment for actin myofilaments

'itin filaments1 elastic chains of amino acids/keep thick and thin filaments in properalignment



Structure of ctin and Myosin



Myosin ('hick)

Myofilament

• Many elongated myosin molecules shapedlike golf clu$s%

• Single filament contains roughly 4**myosin molecules

• Molecule consists of t,o heavy myosinmolecules ,ound together to form a rod portion lying parallel to the myosinmyofilament and t,o heads that e.tendlaterally%

• Myosin heads

;% "an $ind to active sites on the actinmolecules to form cross:$ridges%(ctin $inding site)

=% ttached to the rod portion $y a hingeregion that can $end and straightenduring contraction%

4% &ave 'Pase activity1 activity that $reaks do,n adenosine triphosphate('P)- releasing energy% Part of theenergy is used to $end the hingeregion of the myosin molecule duringcontraction



ctin ('hin)

Myofilaments

• 'hin Filament1 composed of 4 ma3or proteins

;% F (fi$rous) actin

=% 'ropomyosin

4% 'roponin

• ',o strands of fi$rous (F) actin form adou$le heli. e.tending the length of themyofilament/ attached at either end atsarcomere%

"omposed of A actin monomerseach of ,hich has a myosin-binding site (see yello, dot)

ctin site can $ind myosin duringmuscle contraction%

• 'ropomyosin1 an elongated protein,inds along the groove of the F actindou$le heli.%

• 'roponin is composed of three su$units1

'n: 1 $inds to actin

'n:' 1$inds to tropomyosin-

'n:" 1$inds to calcium ions%



5o,- putting it all together to perform the function

of muscle1 "ontraction



? line ? line



& Band



Sarcomere Rela.ed



Sarcomere Partially "ontracted



Sarcomere "ompletely

"ontracted



#indin" Site Tropomyosin

Troponin

Ca$



Myosin



8.citation:"ontraction "oupling

Muscle contraction

•lpha motor neurons release ch•"h produces large 8PSP in muscle fi$ers (vianicotinic ch receptors

•8PSP evokes action potential•ction potential (e.citation) triggers "a=>

release- leads to fi$er contraction•Rela.ation- "a=> levels lo,ered $y organelle

reuptake



Sliding Filament Model of

"ontraction• 'hin filaments slide past the thick ones so

that the actin and myosin filaments overlap

to a greater degree• 0n the rela.ed state- thin and thick filaments

overlap only slightly

• pon stimulation- myosin heads $ind toactin and sliding $egins



The lever movement drives displacement of the actin filament relative to the myosin

head %&' nm(, and by deformin" internal elastic structures, produces force %&' p)(*

Thick and thin filaments interdi"itate and +slide relative to each other*

&o, striated muscle ,orks1 'he Sliding Filament Model



5euromuscular Cunction




• Region ,here the motor neuron stimulates the muscle fi$er • 'he neuromuscular 3unction is formed $y 1

;% 8nd of motor neuron a.on (a.on terminal)• 'erminals have small mem$ranous sacs (synaptic vesicles) that

contain the neurotransmitter acetylcholine ("h)

=% 'he motor end plate of a muscle• specific part of the sarcolemma that contains "h receptors

• 'hough e.ceedingly close- a.onal ends and muscle fi$ersare al,ays separated $y a space called the synaptic cleft




M t it 'h 5 M l



Motor nit1 'he 5erve:Muscle

Functional nit

• motor unit is a motor neuron and all the

muscle fi$ers it supplies

• 'he num$er of muscle fi$ers per motor unit canvary from a fe, (:D) to hundreds (;=**:;E**)

• Muscles that control fine movements (fingers-

eyes) have small motor units• Large ,eight:$earing muscles (thighs- hips) have

large motor units



Motor nit1 'he 5erve:Muscle

Functional nit

• Muscle fi$ers from a motor unit are spread

throughout the muscle 5ot confined to one fascicle

• 'herefore- contraction of a single motor unit causes,eak contraction of the entire muscle

• Stronger and stronger contractions of a musclere7uire more and more motor units $eing stimulated(recruited)

Motor nit



Motor nitAll the muscle cells controlled by one

nerve cell



l h li 9 5



cetylcholine 9pens 5a>

"hannel



Muscle "ontraction Summary

• 5erve impulse reaches myoneural 3unction

• cetylcholine is released from motor

neuron

• ch $inds ,ith receptors in the muscle

mem$rane to allo, sodium to enter

• Sodium influ. ,ill generate an action

potential in the sarcolemma



Muscle "ontraction ("ontd)

• ction potential travels do,n ' tu$ule

• Sarcoplamic reticulum releases calcium

• "alcium $inds ,ith troponin to move the

troponin- tropomyosin comple.

• Binding sites in the actin filament are

e.posed



Muscle "ontraction (contd)

• Myosin head attach to $inding sites and

create a po,er stroke

• 'P detaches myosin heads and energi@esthem for another contaction

• <hen action potentials cease the muscle

stop contracting



"ontraction Speed

M i i h

M i i M l l M t



Myosin is a he-amer.

myosin heavy chains

/ myosin li"ht chains

C terminus n m

Coiled coil of to helices

Myosin is a Molecular Motor

Myosin S1 fra"ment

crystal structure

ue"" et al*, %00(

News Physiol Sci 12.13415*)64terminal catalytic%motor( domain

neck re"ion7lever arm

)ucleotidebindin" site

Myosin head: retains all of the motor functions of myosin,i.e. the ability to produce movement and force.

"hemomechanical coupling – conversion of chemical energy



"hemomechanical coupling conversion of chemical energy

('P a$out G kcal . mole:;) into force2movement%

• 'P is unsta$le thermodynamically

• ',o most energetically favora$le steps1

;% 'P $inding to myosin

=% Phosphate release from myosin

• Rate of cycling determined $y MH'Pase activity and e.ternal load

Adapted from 8oldman 9 #renner %1:52( Ann Rev Physiol /:.;:4;3;*

Shortenin" <elocity <ependent on ATPase Activity



Shortenin" <elocity <ependent on ATPase Activity

!ifferent myosin heavy chains (M&"s) have different 'Pase activities%

'here are at least G separate skeletal muscle M&" genesIarranged in series

on chromosome ;G%

',o cardiac M&" genes located in tandem on chromosome ;%

'he slo, β cardiac M&" is the predominant gene e.pressed in slo, fi$ers

of mammals%

8oldspink %1:::( J Anat 1:/.33433/*

Po,er 9utput1 'he Most Physiologically Relevant



Peak poer obtained at intermediate loads and intermediate

velocities*

Po,er 9utput1 'he Most Physiologically Relevant

Marker of Performance

Poer = ork 7 time= force - distance 7 time

= force - velocity

>i"ure from #erne and ?evy, Physiology

Mosby@ear #ook, Bnc*, 1::3*

'hree Potential ctions !uring Muscle "ontraction1



• shortenin"

• isometric

• len"thenin"

%Bsotonic. shortenin" a"ainst fi-ed

load, speed dependent on

MATPase activity and load(

'hree Potential ctions !uring Muscle "ontraction1

Most likely to cause

muscle inDury

#iceps muscle shortens

durin" contraction

Biceps muscle lengthens

during contraction



Motor nit Ratios

• Back muscles

;1;**

• Finger muscles ;1;*

• 8ye muscles

;1;

Recall The otor !nit"



Recall The otor !nit"motor neuron and the muscle fibers it innervates

Spinalcord • The smallest amount of

muscle that can be activatedvoluntarily*

• 8radation of force in skeletal

muscle is coordinated lar"ely

by the nervous system*

• ecruitment of motor units

is the most important means

of controllin" muscle tension*

To increase force.

1* ecruit more M**s

* Bncrease freF*

%force GfreFuency(

• Since all fibers in the motor

unit contract simultaneously,pressures for "ene e-pression

%e*"* freFuency of stimulation,

load( are identical in all fibers

of a motor unit*

Physiological profiles of motor units"



y g p

all fi$ers in a motor unit are of the same fi$er type

Slo motor units contain slo fibers. • Myosin ith lon" cycle time and therefore uses

ATP at a slo rate*

• Many mitochondria, so lar"e capacity to

replenish ATP*

• Economical maintenance of force durin"

isometric contractions and efficient performance

of repetitive slo isotonic contractions*

>ast motor units contain fast fibers.

• Myosin ith rapid cyclin" rates*

• >or hi"her poer or hen isometric force

produced by slo motor units is insufficient*• Type A fibers are fast and adapted for

producin" sustained poer*

• Type H fibers are faster, but non4o-idative

and fati"ue rapidly*

• H7I not #*

Modified from #urke and Tsairis, Ann N# Aca$ Sci 5.1/'41':, 1:2/

%ncrease$ use" strength training



g g

Early "ains in stren"th appear to be predominantly due to neural

factorsJoptimiKin" recruitment patterns*

?on" term "ains almost solely the result of hypertrophy i*e*

increased siKe*

The P%()*A+t(P')*mT,R pathway is a



ommel et al* %001( Nature &ell 'iology 3, 100:*

crucial regulator o s+eletal muscle

hypertrophy*atrophy .

• Application of B8>4B to CC1

myotube cultures induced both

increased idth and phosphor4

ylation of donstream tar"ets of

Akt %p20S; kinase, p20S;L

P6AS417/E4#P1 8SL3( but did

)NT activate the calcineurin

pathay*

• Treatment ith rapamycin

almost completely prevented

increase in idth of CC1myotubes*

• Treatment ith cyclosporin or

>L'0; does not prevent myotube

"roth in vitro or compensatory

hypertrophy in vivo

• ecovery of muscle ei"ht

after folloin" reloadin" is

blocked by rapamycin but not

cyclosporin*

Performance Declines with Aging



Performance Declines with Aging

--despite maintenance of physical activity

A"e %years(

10 0 30 /0 '0 ;0

P e r f o r m a n c e

% O o

f p e a k (

0

0

/0

;0

50

100

Shotput7Iiscus

Marathon

#asketball %rebounds7"ame(

I*6* Moore %1:2'( Nature '3.;/4;'*

N'A Register/ 1::41::3 Edition

Number o motor units $eclines $uring aging



Number o motor units $eclines $uring aging

- e0tensor $igitorum brevis muscle o humans

Campbell et al*, %1:23( J Neurol Neurosurg Psych 3;.2/415*

A8E4ASSNCBATEIATNP6 IE TN #NT6J

Bndividual fiber atrophy

%hich may be at least

partially preventable andreversible throu"h e-ercise(*

?oss of fibers

%hich as yet appears

irreversible(*

Motor unit remodeling with aging



Motorneuronloss

Centralnervoussystem

g g g

Muscle

• Fewer motor units• More fbers/motor unit

A G

I N G

ean otor !nit 1orces">> t it t ll i ld d d i b



• >> motor units "et smaller in old a"e and decrease in number

• S motor units "et bi""er ith no chan"e in number

• Iecreased rate of force "eneration and PNEQQ

FF FI FR S

M a - i m u m B s o m e t r i c >

o r c e % m ) (

0

!

!0

"!

#00

#!#!0

#"!

00

!

Adult

$ld

Motor nit Classification Ladhiresan et al*, %1::;( J Physiol /:3.'/34''*



• Muscles in old animals are more susceptible to contraction4

induced inDury than those in youn" or adult animals*

uscle in2ury may play a role in the $evelopment o

atrophy with aging.

• Muscles in old animals sho delayed and impaired recovery

folloin" contraction4induced inDury*

• >olloin" severe inDury, muscles in old animals displayprolon"ed, possibly irreversible, structural and functional

deficits*



!isorders of Muscle 'issue

• Muscle tissues e.perience fe, disorders

&eart muscle is the e.ception

Skeletal muscle remarka$ly resistant toinfection

Smooth muscle pro$lems stem from e.ternal

irritants




• Muscular dystrophy a group of inherited

muscle destroying disease

ffected muscles enlarge ,ith fat andconnective tissue

Muscles degenerate

• 'ypes of muscular dystrophy

!uchenne muscular dystrophy

Myotonic dystrophy




• Myofascial pain syndrome pain is caused

$y tightened $ands of muscle fi$ers

• Fi$romyalgia a mysterious chronic:painsyndrome

ffects mostly ,omen

Symptoms fatigue- sleep a$normalities-severe musculoskeletal pain- and headache

uscular 3ystrophy"



• Proteins localiKed in the nucleus, cytosol, cytoskeleton, sarcolemma, and ECM*

Cohn and Campbell %000( uscle Nerve 3.1/':41/21*

• Since the discovery of dystrophin, numerous "enetic disease loci have been linked to protein

products and to cellular phenotypes, "eneratin" models for studyin" the patho"enesis of the

dystrophies*

A freFuently fatal disease of muscle deterioration

• Muscular dystrophies have in the past been classified based on subDective and sometimes

subtle differences in clinical presentation, such as a"e of onset, involvement of particular

muscles, rate of pro"ression of patholo"y, mode of inheritance*

3ystrophin unction"



%Some components ofthe dystrophin "lycoprotein

comple- are relatively

recent discoveries, so one

cannot assume that all

players are yet knon*(

DGC

dystrop%indystro&lycan ' and (sarco&lycans ' ) ) γ) δ(syntrop%ins '

) #(dystrobrevins ' ) (sarcospanlaminin* 'merosin(

Cohn and Campbell %000( uscle Nerve 3.1/':41/21*

transmission o orce to e0tracellular matri0

9 idati e and Al col tic Fi$ers



9.idative and Alycolytic Fi$ers



'P



"reatine

• Molecule capa$le of storing 'P energy

"reatine > 'P "reatine phosphate > !P



"reatine Phosphate

• Molecule ,ith stored 'P energy

"reatine > 'P"reatine phosphate > !P



Muscle Fatigue

• Lack of o.ygen causes 'P deficit

• Lactic acid $uilds up from anaero$ic

respiration

M l F ti



Muscle Fatigue



Muscle trophy

• <eakening and shrinking of a muscle

• May $e caused

0mmo$ili@ation

Loss of neural stimulation



Muscle &ypertrophy

• 8nlargement of a muscle

• More capillaries

• More mitochondria• "aused $y

Strenuous e.ercise

Steroid hormones



Steroid &ormones

• Stimulate muscle gro,th and hypertrophy



Muscle 'onus

• 'ightness of a muscle

• Some fi$ers al,ays contracted



'etany

• Sustained contraction of a muscle

• Result of a rapid succession of nerve

impulses



'etanus



Refractory Period

• Brief period of time in ,hich muscle cells

,ill not respond to a stimulus



Refractory



Skeletal Muscle "ardiac Muscle

Refractory Periods



0sometric "ontraction

• Produces no movement

• sed in

Standing

Sitting

Posture



0sotonic "ontraction

• Produces movement

• sed in

<alking

Moving any part of the $ody



Muscle Spindle

Muscle Spindle Responses



p p

lpha 2 Aamma "oactivation



lpha 2 Aamma "oactivation

Aolgi 'endon 9rgans



Aolgi 'endon 9rgans

!evelopmental spects1



Regeneration

• "ardiac and skeletal muscle $ecome amitotic- $ut canlengthen and thicken

• Myo$last:like satellite cells sho, very limitedregenerative a$ility

• "ardiac cells lack satellite cells• Smooth muscle has good regenerative a$ility

• 'here is a $iological $asis for greater strength in men thanin ,omen

• <omens skeletal muscle makes up 4D+ of their $odymass

• Mens skeletal muscle makes up =+ of their $ody mass

!e elopmental spects1



!evelopmental spects1

Male and Female• 'hese differences are due primarily to the

male se. hormone testosterone

• <ith more muscle mass- men are generallystronger than ,omen

• Body strength per unit muscle mass-

ho,ever- is the same in $oth se.es

!evelopmental spects1 ge



!evelopmental spects1 ge

Related• <ith age- connective tissue increases and muscle

fi$ers decrease

• Muscles $ecome stringier and more sine,y

• By age J*- E*+ of muscle mass is lost(sarcopenia)

• !ecreased density of capillaries in muscle

• Reduced stamina• 0ncreased recovery time

• Regular e.ercise reverses sarcopenia

Skeletal Muscle (Extra Reference)

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Transcript of Skeletal Muscle (Extra Reference)