Skeletal Muscle Physiology

Muscular System Functions

Body movement (Locomotion) Maintenance of posture Respiration
Diaphragm 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
.n the *alls of hollo* organs+ "lood vessels+ eye+ glands+ uterus+ skin Some functions/ propel urine+ mi, food in digestive tract+ dilating0constricting pupils+ regulating "lood flo*+ .n some locations+ autorhythmic ontrolled involuntarily "y endocrine and autonomic nervous systems

Cardiac
$eart/ ma1or source of movement of "lood &utorhythmic ontrolled involuntarily "y endocrine and autonomic nervous systems

Muscle %issue %ypes

Connective Tissue Sheaths

onnective %issue of a Muscle
Epimysium# Dense 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 of muscle fi"ers called a fascicle
ontains "#v and nerves

Endomysium# Loose connective individual muscle fi"ers

tissue

that

surrounds

&lso contains "#v#+ nerves+ and satellite cells (em"ryonic stem cells function in repair of muscle tissue

ollagen fi"ers of all 2 layers come together at each end of muscle to form a tendon or aponeurosis.

3ross &natomy

4ach skeletal muscle is *rapped "y 2 concentric layers of connective tissue#

Epi-, Peri-, and Endomysium

Are interwoven - Go over into tendon Distinguish between:

%endon &poneurosis Ligament

unction:

Protection Blood supply .nnervation

5erve and Blood !essel Supply

!"eletal #uscles are rich in nerves and blood vessels Che#ical co##unication at !ynapsis $neuro#uscular %unction& !ynaptic ter#inal of axon #eets #otor end plate of #uscle cell Coiled capillaries are able to adapt to changes in length of #uscle fiber

5erve and Blood !essel Supply

Motor neurons
stimulate muscle fi"ers to contract 5euron a,ons "ranch so that each #uscle fiber (muscle cell) is innervated Form a neuromuscular 1unction (6 myoneural 1unction)

apillary "eds surround muscle fi"ers Muscles re7uire large amts of energy 4,tensive vascular net*ork delivers necessary o,ygen and nutrients and carries a*ay meta"olic *aste produced "y muscle fi"ers

Skeletal Muscle
Long cylindrical cells Many nuclei per cell Striated (tiny "ands that run across the muscle cells) !oluntary Rapid contractions (most rapid of the muscle types)

Basic Features of a Skeletal Muscle

Muscle attachments
Most skeletal muscles run from one "one to another 8ne "one *ill move 9 other "one remains fi,ed 8rigin 9 less mova"le attach: ment .nsertion 9 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 9 connective tissue fi"ers are short .ndirect attachments 9 connective tissue forms a tendon 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 (;(:;(( m)+ cylindrical+ and multinucleated %end to "e smaller diameter in small muscles and larger in large muscles# ; mm: ' cm in length Develop from myo"lasts- num"ers remain constant Striated appearance 5uclei are peripherally located

Muscle &ttachments

Microanatomy of Skeletal Muscle Fi"ers

!o#e vocabulary: Skeletal muscle fi"er or myofi"er Sarcolemma Sarcoplasm Sarcoplasmic reticulum Myofi"ril Myofilaments

Microanatomy of Skeletal Muscle

4ach muscle cell is called a muscle fi"er/ & fi"er "undle contains hundreds of myofi"rils that run the length of the fi"er# <ithin each fi"er are myofi"rils# 4ach myofi"ril linear array sarcomeres muscle many is a of

Myofilaments

Myofi"er ( ;((=m)

Myofi"rils (

;:> =m)

Myofilaments &ctin ? Myosin

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 the surface Filled *ith e,tracellular fluid Myofibrils (; m):cylindrical structures *ithin muscle fi"er &re "undles of protein filaments (6myofilaments) %*o types of myofilaments ;# &ctin filaments (thin filaments : @nm) ># Myosin filaments (thick filaments 9 ;@nm) &t each end of the fi"er+ myofi"rils are anchored to the inner surface of the sarcolemma <hen myofi"ril shortens+ muscle shortens (contracts)

 SR is an ela"orate+ smooth endoplasmic reticulum

net*ork of tu"ules ? sacs- runs longitudinally and surrounds each myofi"ril enlarged ? fused at 1unction "et*een & ? . "ands/ transverse sacs : Form cham"ers : also called ter#inal cisternae : on either side of the %:tu"ules

Sarcoplasmic Reticulum (SR)

& single %:tu"ule and the > terminal cisternae form a triad % system/ duct for fluids ? propogation of electrical stimulus for contraction (action potential) SR stores aAA *hen muscle not contracting
<hen stimulated+ calcium released into sarcoplasm SR mem"rane has aAA pumps that function to pump aAA out of the sarcoplasm "ack into the SR after contraction

Sarcoplasmic Reticulum (SR)

Sarcomeres
'hic" and 'hin ila#ents are organi(ed in repeating functional units ) ****** Each #yofibril has linear arrange#ent of ,-.--- sarco#ers +

/anded appearance $striation& due to arrange#ent of thic" and thin fila#ents 0nteraction of thic" and thin fila#ents responsible for s"eletal #uscle fiber contraction

Sarcomere Structure

. : "and 6 L.ght "and

&: "and 6 d&rk "and

B : line

Sarcomere : repeating functional units of a myofi"ril

bout !",""" sarcomeres per myofibril, end to end Each is about # $m lon%

Sarcomeres/ B Disk to B Disk

4ach sarcomere is capped on ends "y a transverse tu"ule (t:tu"ule) that is an e,tension of sarcolemmal mem"rane Surfaces of sarcomeres are covered "y SR Differences in siCe+ density+ and distri"ution of thick and thin filaments gives the muscle fi"er a "anded or striated appearance#
& "ands/ a dark "and- full length of thick (myosin) filament in central of sarcomere M line : transverse ? longitudinally oriented linking protein to *hich myosins attach $ Cone : thick "ut 58 thin filaments- gap "et*een ends of thin filaments in center of & "and . "ands/ a light "and- from B disks to ends of thick filaments
%hin "ut 58 thick filaments 4,tends from & "and of one sarcomere to & "and of the ne,t sarcomere

B disk/ filamentous net*ork of protein# Serves as attachment for actin myofilaments %itin filaments/ elastic chains of amino acids- keep thick and thin filaments in proper alignment

Parts of a Muscle

Myosin (%hick) Myofilament

Many elongated myosin molecules shaped like golf clu"s# Single filament contains roughly 2(( myosin molecules Molecule consists of t*o heavy myosin molecules *ound together to form a rod portion lying parallel to the myosin myofilament and t*o heads that e,tend laterally# Myosin heads ;# an "ind to active sites on the actin molecules to form cross:"ridges# (&ctin "inding site) ># &ttached to the rod portion "y a hinge region that can "end and straighten during contraction# 2# $ave &%Pase activity/ activity that "reaks do*n adenosine triphosphate (&%P)+ releasing energy# Part of the energy is used to "end the hinge region of the myosin molecule during contraction

%hick Filament/ Myosin

Structure of %hick Filaments

1yosin - 2 heavy chains. 3 light chains $eavy chains : >2( kD each Light chains : > pairs of different >( kD chains %he DheadsD of heavy chains have &%Pase activity and hydrolysis here drives contraction Light chains are homologous to calmodulin and also to %n See structure of heads in Figure ;E#;F

Repeating 4lements in Myosin

'he secret to ultrastructure E:residue+ >G:residue and ;HF:residue repeats are responsi"le for the organiCation of thick filaments Residues ; and ' (a and d) of the seven: residue repeat are hydropho"ic- residues >+2 and F ("+ c and f) are ionic %his repeating pattern favors formation of coiled coil of tails# (<ith 2#F : 58% 2#@ : residues per turn+ a:helices *ill coilI)

More RepeatsI
>G:residue repeat (' , E) consists of distinct patterns of alternating side:chain charge (A vs :)+ and these regions pack *ith regions of opposite charge on ad1acent myosins to sta"iliCe the filament ;HF:residue repeat (E , >G) pattern also contri"utes to packing and sta"ility of filaments

%hin Filament/ composed of 2 ma1or proteins ;# F (fi"rous) actin ># %ropomyosin 2# %roponin %*o strands of fi"rous (F) actin form a dou"le heli, e,tending the length of the myofilament- attached at either end at sarcomere# omposed of 3 actin monomers each of *hich has a #yosin-binding site (see yello* dot) &ctin site can "ind myosin during muscle contraction# F:actin heli, has a pitch of E> nm But repeat distance is 2F nm %ropomyosin/ an elongated protein heterodimers+ *inds along the groove of the F actin dou"le heli,# %roponin is composed of three su"units/ %n:& / "inds to actin %n:% /"inds to tropomyosin+ %n: /"inds to calcium ions#

&ctin (%hin) Myofilaments

%hin Filament/ &ctin

F:actin 3:actin

Structure of &ctin and Myosin

5o*+ putting it all together to perform the function of muscle/ ontraction

$ Band

Sliding Filament Model of ontraction

Relative movement of actin ? myosin filaments yields active sarcomere shortening Jpon stimulation+ myosin heads "ind to actin and sliding "egins Myosin heads or cross:"ridges generate contraction force Sliding of actin filaments to*ard center of sarcomere/ decrease in . "and and decrease in $ Cone as B lines move closer %hin filaments slide past the thick ones so that the actin and myosin filaments overlap to a greater degree .n the rela,ed state+ thin and thick filaments overlap only slightly

$o* striated muscle *orks/ %he Sliding Filament Model

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+

& small section of a myofi"ril is illustrated here/ %he thick myosin filaments are arranged "et*een overlapping actin filaments# %he t*o B lines mark the "oundary of a sarcomere# %he sarcomere is the functional unit of a muscle cell

B line

B line

Sarcomere Rela,ed

& "and/ .t is formed "y "oth myosin and actin filaments# %he part of the sarcomere *ith only actin filaments is called the . "and# %his is a sarcomere that is rela,ed#

Sarcomere Partially ontracted

%his sarcomere is partially contracted# 5otice than the . "ands are getting shorter#

Sarcomere ompletely ontracted

%he sarcomere is completely contracted in this slide# %he . and $ "ands have almost disappeared#

<hich filament has moved as the sarcomere contractedK 5ote the thick myosin filaments have not changed+ "ut the thin actin filaments have moved closer together#

 %he actin filaments are moved "y the heads of the myosin filaments# .n step one the myosin head attaches to an actin filament to create a cross "ridge# Step t*o sho*s that the attached myosin head "ends to move the actin filament# %he myosin head as e,pended energy to create this movement# %his is a po*er stroke or *orking stroke# Step three sho*s that energy in the form of &%P *ill unhook the myosin head# .n step ' the myosin head is cocked and ready to attach to an actin filament to start another po*er stroke#

L%he string of green circles represents an actin filament# %here are "inding sites in the filament for the attachment of myosin heads# L.n a rela,ed muscle the "inding sites are covered "y tropomyosin# %he tropomyosin has molecules of troponin attached to it# L alcium+ sho*n in yello*+ *ill attach to troponin# L alcium *ill change the position of the troponin+ tropomyosin comple,# L%he troponin+ tropomyosin comple, has no* moved so that the "inding sites are no longer covered "y the troponin+ tropomyosin comple,#

.indin% Site

Ca#/

Tropomyosin

Troponin

%he "inding sites are no* e,posed and myosin heads are a"le to attach to form cross "ridges#L

Myosin

%his diagram sho*s the microanatomy of skeletal muscle tissue again# L%he "lue sarcoplasmic reticulum is actually the endoplasmic reticulum# .t stores calcium# L%he mitochondria are illustrated in orange# %hey generate &%P+ *hich provides the energy for muscle contractions#

%hree %ypes of Muscle Fi"ers

,& ast $or 4hite& ibers
ast contraction after nervous sti#ulation 5arge dia#eter large glycogen reserve fe* mitochondria densely packed myofi"rils atigue fast due to #ainly anaerobic respiration

>) Slo* (or Red) Fi"ers

!lower but continuous contraction for extended periods !#aller dia#eter $+ half& contain myoglo"in more capillaries more mitochondria

Do not fatigue as fast due to 6

2) .ntermediate Fi"ers
7ave attributes in between fast and slow types 1ost s"eletal #uscles contain #ixture of fiber types.

Proportion of ***********6

fast

to

slow

depends

on

8ne #otor unit only contains one fiber type Eye. hand: **** fibers do#inate /ac". calf: **** fibers do#inate

Muscle Differentiation (types of fi"ers)

I (slow-twitch oxidative) Contraction speed Myosin-ATPase activity Pri ary so!rce of ATP prod!ction $lycolytic en%y e activity 'o( of itochondria Capillaries Myoglo#in contents M!scle Color $lycogen content )i#er dia eter *ate of fatig!e Slow Low "xidative phosphorylation Low Many Many High *ed Low s all slow IIA (fast-twitch oxidative glycolytic) fast High "xidative phosphorylation &nter ediate Many Many High *ed &nter ediate &nter ediate &nter ediate IIB fast-twitch glycolytic fast High Anaero#ic glycolysis High )ew )ew Low +hite High Large )ast (0

4,citation: ontraction oupling

Muscle contraction &lpha motor neurons release &ch & h produces large 4PSP in muscle fi"ers (via nicotinic &ch receptors) 4PSP evokes action potential &ction potential (e,citation) triggers a>A release+ leads to fi"er contraction Rela,ation+ a>A levels lo*ered "y organelle reuptake

4,citation: ontraction oupling

4,citation: ontraction oupling

5euromuscular Munction
Region *here the motor neuron stimulates the muscle fi"er %he neuromuscular 1unction is formed "y / ;# 4nd 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"ers are al*ays separated "y a space called the synaptic cleft

5euromuscular Munction

5euromuscular Munction

Motor Jnit/ %he 5erve:Muscle Functional Jnit

& motor unit is a motor neuron and all the muscle fi"ers it supplies %he num"er of muscle fi"ers per motor unit can vary from a fe* (':F) to hundreds (;>((: ;@(() Muscles that control fine movements (fingers+ eyes) have small motor units Large *eight:"earing muscles (thighs+ hips) have large motor units

Motor Jnits
) All #uscle fibers that are controlled by a single #otor neuron

'he lower the ratio of #uscle fibers to neurons. the #ore precise the #ove#ent can be9
ew cases ,: , relationship. 4here6 1ost cases: #any #uscle fibers $up to 2.---& : , #otor neuron. 4here6

Motor Jnit/ %he 5erve:Muscle Functional Jnit

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 muscle re7uire more and more motor units "eing stimulated (recruited&

Motor Jnit
ll the muscle cells controlled by one nerve cell

&cetylcholine 8pens 5a hannel

Muscle ontraction Summary

5erve impulse reaches myoneural 1unction &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 ( ontNd)

&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 (contNd)

Myosin head attach to "inding sites and create a po*er stroke &%P detaches myosin heads and energiCes them for another contaction <hen action potentials cease the muscle stop contracting

ontraction Speed

Myosin is a Molecular Motor

Coiled coil of t4o helices

Myosin is a he1amer2 # myosin heavy chains 3 myosin li%ht chains

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

*8#-terminal catalytic &motor) domain

# nm
C terminus

Myosin S! fra%ment crystal structure

neck re%ion9lever arm 5ue%% et al+, &#""#) News Physiol Sci !02#!6-#!7+

hemomechanical coupling conversion of chemical energy

(&%P a"out E kcal , mole:;) into force0movement#

&%P is unsta"le thermodynamically %*o most energetically favora"le steps/

;# &%P "inding to myosin ># Phosphate release from myosin Rate of cycling determined "y MO&%Pase activity and e,ternal load
dapted from :oldman ; .renner &!<70) Ann Rev Physiol 3<2=#<-=6=+

Shortenin% >elocity >ependent on TPase ctivity

Different myosin heavy chains (M$ s) have different &%Pase activities# %here are at least E separate skeletal muscle M$ genesParranged in series on chromosome ;E# %*o cardiac M$ genes located in tandem on chromosome ;'# %he slo* cardiac M$ is the predominant gene e,pressed in slo* fi"ers of mammals#

:oldspink &!<<<) J Anat !<326#6-663+

Po*er 8utput/ %he Most Physiologically Relevant Marker of Performance

Po4er ? 4ork 9 time ? force 1 distance 9 time ? force 1 velocity

Peak po4er obtained at intermediate loads and intermediate velocities+ @i%ure from .erne and Aevy, Physiology
MosbyBCear .ook, Dnc+, !<<6+

%hree Potential &ctions During Muscle ontraction/

shortenin%
.iceps muscle shortens durin% contraction

&Dsotonic2 shortenin% a%ainst fi1ed load, speed dependent on ME TPase activity and load)

isometric

len%thenin%

Biceps muscle lengthens during contraction

Most likely to cause muscle inFury

Motor Jnit Ratios

Back muscles
;/;((

Finger muscles
;/;(

4ye muscles
;/;

Recall The
Spinal cord

otor !nit"
The smallest amount of muscle that can be activated voluntarily+ :radation of force in skeletal muscle is coordinated lar%ely by the nervous system+ 5ecruitment of motor units is the most important means of controllin% muscle tension+ Since all fibers in the motor unit contract simultaneously, pressures for %ene e1pression &e+%+ freHuency of stimulation, load) are identical in all fibers of a motor unit+

motor neuron and the muscle fibers it innervates

To increase force2 !+ 5ecruit more M+G+s #+ Dncrease freH+ &force freHuency)

Physiological profiles of motor units" all fi"ers in a motor unit are of the same fi"er type
Slo4 motor units contain slo4 fibers2
Myosin 4ith lon% cycle time and therefore uses TP at a slo4 rate+ Many mitochondria, so lar%e capacity to replenish TP+ Economical maintenance of force durin% isometric contractions and efficient performance of repetitive slo4 isotonic contractions+

@ast motor units contain fast fibers2

Myosin 4ith rapid cyclin% rates+ @or hi%her po4er or 4hen isometric force produced by slo4 motor units is insufficient+ Type # fibers are fast and adapted for producin% sustained po4er+ Type #I fibers are faster, but non-o1idative and fati%ue rapidly+ #I9#J not #.+
Modified from .urke and Tsairis, Ann N# Aca$ Sci ##72!3(-!(<, !<03+

%ncrease$ use" strength training

Early %ains in stren%th appear to be predominantly due to neural factorsKoptimiLin% recruitment patterns+ Aon% term %ains almost solely the result of hypertrophy i+e+ increased siLe+

The P%(())*A+t(P)')*mT,R pathway is a crucial regulator o- s+eletal muscle hypertrophy*atrophy.

pplication of D:@-D to C#C!# myotube cultures induced both increased 4idth and phosphorylation of do4nstream tar%ets of kt &p0"S= kinase, p0"S=MN P8 S-!93E-.P!N :SM6) but did *OT activate the calcineurin path4ay+ Treatment 4ith rapamycin almost completely prevented increase in 4idth of C#C!# myotubes+ Treatment 4ith cyclosporin or @M("= does not prevent myotube %ro4th in vitro or compensatory hypertrophy in vivo 5ecovery of muscle 4ei%ht after follo4in% reloadin% is blocked by rapamycin but not cyclosporin+

5ommel et al+ &#""!) Nature &ell 'iology 6, !""<+

Performance Performance Declines Declines with with Aging Aging --despite --despite maintenance maintenance of of physical physical activity activity
!"" Performance &P of peak) 7" =" 3" #" " !"
Shotput9Jiscus Marathon .asketball &rebounds9%ame)

#"

6"

3"

("

="

%e &years)
J+8+ Moore &!<0() Nature #(62#=3-#=(+ N'A Register/ !<<#-!<<6 Edition

Number o- motor units $eclines $uring aging - e0tensor $igitorum brevis muscle o- humans
:E- SSOCD TEJ T5OP8C JGE TO .OT8K Dndividual fiber atrophy &4hich may be at least partially preventable and reversible throu%h e1ercise)+ Aoss of fibers &4hich as yet appears irreversible)+

Campbell et al+, &!<06) J Neurol Neurosurg Psych 6=203-!7#+

Motor Motor unit unit remodeling remodeling with with aging aging
Central nervo!s syste M!scle

Motor ne!ron loss

A$&'$

, )ewer otor !nits , More fi#ers- otor !nit

ean

otor !nit 1orces"

@@ motor units %et smaller in old a%e and decrease in number S motor units %et bi%%er 4ith no chan%e in number Jecreased rate of force %eneration and POQE5RR
//0

Ma1imum Dsometric @orce &m*)

/.. 210 20. 2/0 2.. 10 0. /0 .

Ad!lt "ld

))

Motor Gnit Classification

)&

)*

Madhiresan et al+, &!<<=) J Physiol 3<62(36-((#+

uscle in2ury may play a role in the $evelopment oatrophy with aging.
Muscles in old animals are more susceptible to contractioninduced inFury than those in youn% or adult animals+

Muscles in old animals sho4 delayed and impaired recovery follo4in% contraction-induced inFury+ @ollo4in% severe inFury, muscles in old animals display prolon%ed, possibly irreversible, structural and functional deficits+

Disorders of Muscle %issue

Muscle tissues e,perience fe* disorders
$eart muscle is the e,ception Skeletal muscle 9 remarka"ly resistant to infection Smooth muscle 9 pro"lems stem from e,ternal irritants

Disorders of Muscle %issue

Muscular dystrophy 9 a group of inherited muscle destroying disease
&ffected muscles enlarge *ith fat and connective tissue Muscles degenerate
%ypes of muscular dystrophy Duchenne muscular dystrophy Myotonic dystrophy

Disorders of Muscle %issue

Myofascial pain syndrome 9 pain is caused "y tightened "ands of muscle fi"ers Fi"romyalgia 9 a mysterious chronic: pain syndrome
&ffects mostly *omen Symptoms 9 fatigue+ sleep a"normalities+ severe musculoskeletal pain+ and headache

uscular 3ystrophy"
freHuently fatal disease of muscle deterioration
Muscular dystrophies have in the past been classified based on subFective 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+ 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+ Proteins localiLed in the nucleus, cytosol, cytoskeleton, sarcolemma, and ECM+

Cohn and Campbell &#""")

uscle Nerve #62!3(<-!30!+

3ystrophin -unction" transmission o- -orce to e0tracellular matri0

3$C
dystrophin dystroglycan ( and ) sarcoglycans (4 4 4 ) syntrophins (4 2) dystro#revins (4 ) sarcospan la inin-/ ( erosin)

&Some components of the dystrophin %lycoprotein comple1 are relatively recent discoveries, so one cannot assume that all players are yet kno4n+)
Cohn and Campbell &#""") uscle Nerve #62!3(<-!30!+

8,idative and 3lycolytic Fi"ers

&%P

reatine
Molecule capa"le of storing &%P energy reatine A &%P

reatine phosphate A &DP

reatine Phosphate
Molecule *ith stored &%P energy reatine phosphate A &DP reatine A &%P

Muscle Fatigue
Lack of o,ygen causes &%P deficit Lactic acid "uilds up from anaero"ic respiration

Muscle Fatigue

Muscle &trophy
<eakening and shrinking of a muscle May "e caused
.mmo"iliCation Loss of neural stimulation

Muscle $ypertrophy
4nlargement 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

Refractory Periods

Skeletal Muscle

ardiac Muscle

.sometric ontraction
Produces no movement Jsed in
Standing Sitting Posture

.sotonic ontraction
Produces movement Jsed in
<alking Moving any part of the "ody

Muscle Spindle

Muscle Spindle Responses

&lpha 0 3amma oactivation

3olgi %endon 8rgans

Developmental &spects/ Regeneration

ardiac and skeletal muscle "ecome amitotic+ "ut can lengthen and thicken Myo"last:like satellite cells sho* very limited regenerative a"ility ardiac cells lack satellite cells Smooth muscle has good regenerative a"ility %here is a "iological "asis for greater strength in men than in *omen <omenNs skeletal muscle makes up 2F) of their "ody mass MenNs skeletal muscle makes up '>) of their "ody mass

Developmental &spects/ Male and Female

%hese differences are due primarily to the male se, hormone testosterone <ith more muscle mass+ men are generally stronger than *omen Body strength per unit muscle mass+ ho*ever+ is the same in "oth se,es

Developmental &spects/ &ge Related

<ith age+ connective tissue increases and muscle fi"ers decrease Muscles "ecome stringier and more sine*y By age G(+ @() of muscle mass is lost (sarcopenia) Decreased density of capillaries in muscle Reduced stamina .ncreased recovery time Regular e,ercise reverses sarcopenia