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Whatisphysiology?
Thestudyofnormalfunctioninalivingstate,
Whatisexercisephysiology?
Thestudyofacuteresponsesandchronicadaptationstoexercise.
Someexercisephysiologistsstudytheaffectsofexerciseonpathology.
Thiscanbeverydifferentinindividualsduetotrainingstatusandathlete
types.(strengthvsendurance)
MUSCLE
MuscleàFascicleàFibre(cell)àMyofibrilàSarcomere
ConnectiveTissueLayers
Fascia–superficial(underskin),encapsulatesallbodytissues(eg.Muscleand
bone)
Epimysium–Surroundsindividualwholemuscles,itisthick.
Perimysium–Surroundseachfascicle,containsbloodvessels,motoraxons
andmusclespindles.
Endomysium–surrounds1-2musclefibres,providesbasementmembrane
(frameworkforregeneration)
Sarcolemma=cell/fibremembrane(lipidbilayer)
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Aboveis1sarcomere.Thisshowsthecontractileelementofactinandmyosin
thatcausemusclecontraction
Thestep-wiseprocessofeacheventsequencethatleadstoskeletalmuscle
contraction.
1.Neuromuscularcontraction
2.Excitation-contractioncoupling
3.Cross-bridgecycle
Step1:NeuromuscularTransmission
Themotorunitconsistsofasomaticmotoneuronandthemusclefibresit
innervates.Thereisasynapsecausedbyaactionpotentialbetweenthe
motoneuronandmusclefibreattheneuromuscularjunctionwhichoccursat
themotor-end-plate.Theactionpotentialopensvoltagegatedcalcium
channelswhichcausesthereleaseofacetylcholine(ACh).AChthendiffuses
acrossandbindswithareceptoronthemusclecell.TheNicotiniccholinergic
receptorsallowforaninflowofsodiumandoutflowofpotassiumwhich
generatesacurrentacrossthemembranewithinthemotorendplate.When
thiscurrentgetsbigenoughitwilldriftoutsidethemotorendplateandcause
anactionpotentialwithinamusclecell.
t
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Summary;
Theactionpotentialwillthenrunalongthesurfaceofthecellmembraneand
deepintothecellthroughTransversetubules(T-tubules)whicharelocated
alongsidethezlinesofthesarcomere.TheTtubulesfunctiontorapidlyand
evenlydistributeactionpotentials.Calciumionsarestoredinthesarcoplasmic
reticulumofthemusclecellwhichisamembranenetworksurroundingeach
myofibril.Thesehavetwodistinctregions.Firstlytheterminalcisternaewhich
aresaclikestructuresneartheZ-line/I-bandwhichreleasescalciumintothe
cytosolandformaTRIADwiththeT-tubules.Thesecondregionisthe
LongitudinaltubuleswhicharelocatedneartheA-bandandareresponsible
fortheuptakeofcalcium.
TransverseTubules(T-tubules)
• Invaginationsofthesarcolemmathatappearlikeperforatingholes
• Penetratedeepintoeachmusclefibreallowingactionpotentialsto
quicklyreacheachmyofibrilandthereforesarcomere.
• Thereare2persarcomere,atA-Ijunctions.
SarcoplasmicReticulum(Ca2Storage)
• Membranenetworksurroundingeachmyofibril
• Twodistinctregions
o TerminalCisternae–saclikestructuresneartheZ-line/I-band
thatreleaseCa2intocytosolandformsaTRIADwiththeTtubules.
o Longitudinaltubules–locatedaroundtheA-bandregionand
responsibleforuptakeofCa2fromcytosol.
Step2:Exciting-ContractionCoupling
Theprocessofactionpotentialtransductiontoprovideanintracellularsignal
(increasedCa2)andsubsequentmusclecellcontraction
ThisprocessfocusesmostcommonlyonthelinkbetweentheT-tubuleand
sarcoplasmicreticulumcalciumrelease.Themechanismisnotentirely
understoodbutmuchmoreisunderstoodaboutthefunctionandinteraction
ofkeycomponentsincludingtheT-tubulevoltagesensor(Dihydropyridine
receptor–DHP)andSRCa2channelreleasemechanism(Ryanodinereceptor).
Wheneveraproteindetectssomethingitchangesitstructure,thereforewhen
theDHPreceptorsdetectaactionpotentialtheywillchangetheirstructure
whichwillthencausethecalciumgatedchannels(ryanodinereceptors)to
open.Calciumisthenreleasedintothecell.
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Step2Complete–theintracellularmusclefibreenvironmentnowhasahigh
calciumconcentrationwhichcantriggermyofilamentinteractionstoproduce
forceandcellshortening.
TheMyofilaments/ContractileProteins
Thethickmyosinfilamentiscentrallylocatedwithinthesarcomereandmade
upofaround300smallermyosinmolecules.Thesehaveaprotrudinghead
segmentwhichcontainactinbindingsites.Thetailsegmenthasflexiblehinge
regionsandallcombinetoformthemyofilament.(ImageBelowLeft).
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ThethinactinfilamentareconnectedtoZ-linesatoneendandapparentfree
floatingendislocatedcentrally.Tropomyosinliesoverthemyosinbinding
sitespreventingconstantcontraction.Thetroponincomplexregulatesthe
abilityforthemuscletocontract.Partofthistroponincomplexhastheability
tobindtocalcium.Whenthishappenstropomyosintwistsaroundtheactin
filament,andexposesthemyosinbindingsites.(ImageAboveRight).
Musclestensionorforceisproducedonlywhenmyosinreleasesenergy
obtainedviaATPhydrolysis,andactinandmyosinexistinaboundstate.This
processformsthebasisoftheslidingfilamenttheoryandismostcommonly
describedbythecross-bridgecyclewhichdescribestheinteractionsbetween
themyofilamentcontractileproteins,intracellularCa2ionsandATPhydrolysis.
ForceProduction-FourMajorSteps
• Rest:myosinisinanenergizedstatefollowingATPhydrolysis
• Bound:Actinandmyosinbindatspecificsites
• PowerStroke:energyreleaseand“cellshortening”
• Detachment:ActinandmyosindetachfollowingATPbinding
Step3–Thecrossbridgecycle
1. Atrestmyosinisenergized,ATPhasbeencleavedtoADP,P,andenergy,
energyisstoredwithinthemyosinprotein.
2. Ca2bindstotroponin-C
3. Themyosinbindingsiteonactinbecomesexposed
4. Myosinbecomesboundtoactin
5. Piisreleasedfrommyosinuponbindingwithactin
6. Myosinreleasesenergythroughthepowerstroke
7. Actinisdraggedtowardstheinteriorofthesarcomere–thisappearance
providesthebasisofslidingfilamenttheory
8. Sarcomerelengthincreases,translationtowholemuscleshorteningor
CONTRACTION
9. ADPisreleasedfrommyosinduringthepowerstroke
10.AfterpowerstrokemyosinbindsanewmoleculeofATP
11.Actinandmyosindetach
12.ATPhydrolysisoccurstore-energisemyosin
13.Myosinheadreturnstotheresting“cranked”position
14.IfahighCa2ismaintainthecrossbridgecyclecontinues
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Summary
1.AttheneuromuscularjunctionanactionpotentialisreleasedviaAChwithin
themotorendplate.Thiscausesandinflowofsodiumandanoutflowof
potassiumgeneratingacurrent.
2.Whenthiscurrentisbigenoughtheactionpotentialwilltraveloutsidethe
motorendplateanddownT-tubulesinthesarcoplasmicreticulum.
3.Voltagesensorsarethenactivatedandcalciumisreleasedintothemuscle
cell.
4.Calciumbindstothetroponinofactinfilamentscausingtropomyosinto
twistaroundtheactinfilamentandexposemyosinbindingsites.
5.Crossbridgecyclethenoccursasmyosinmoleculeheadsbindwiththe
myosinbindingsiteontheactin,pullingactinfilamentstogetherand
shorteningthesarcomere.
6.ActiveCa2removalthencausesmusclerelaxation.
7.Returntorestingstate.Thiscrossbridgecycleprocesswillcontinueifaction
potentialscontinue.