骨骼肌生理-夏強(qiáng) 醫(yī)學(xué)課件 浙江大學(xué)醫(yī)學(xué)院英文課件

SkeletalMuscleQiangXIA(夏強(qiáng)),PhDDepartmentofPhysiologyRmC518,BlockC,ResearchBuilding,SchoolofMedicineTel:88208252Email:xiaqiang@Coursewebsite:51/physiologyTypesofmuscle:SkeletalmuscleCardiacmuscleSmoothmuscleStriatedmuscleMuscleTheslidingfilamentmechanism,inwhichmyosinfilaments

bindtoandmoveactinfilaments,isthebasisforshortening

ofstimulatedskeletal,smooth,andcardiacmuscles.Inallthreetypesofmuscle,myosinandactininteractionsare

regulatedbytheavailabilityofcalciumions.Changesinthemembranepotentialofmusclesarelinked

tointernalchangesincalciumrelease(andcontraction).Muscle(cont.)Neuronalinfluencesonthecontractionofmusclesis

affectedwhenneuralactivitycauseschangesinthe

membranepotentialofmuscles.Smoothmusclesoperateinawidevarietyofinvoluntary

functionssuchasregulationofbloodpressureand

movementofmaterialsinthegut.Muscle(cont.)StructureofskeletalmuscleSkeletalmusclesareattachedtotheskeletonbytendons.Skeletalmusclestypicallycontainmany,manymusclefibers.Thesarcomereiscomposedof:thickfilamentscalledmyosin,anchoredinplacebytitinfibers,andthinfilamentscalledactin,anchoredto

Z-lines.Acrosssectionthroughasarcomereshowsthat:eachmyosincaninteractwith6actinfilaments,andeachactincaninteractwith3myosinfilaments.Sarcomerestructuresinanelectronmicrograph.FilamentsMyosinfilament(thickfilament)MyosinActinfilament(thinfilament)ActinTropomyosinTroponinTitinSarcotubularsystem(1)TransverseTubule(2)LongitudinalTubule

SarcoplasmicreticulumMolecularmechanismsofcontractionSliding-filamentmechanismContraction(shortening):

myosinbindstoactin,andslidesit,pullingthe

Z-linesclosertogether,andreducingthewidthofthe

I-bands.Notethatfilamentlengthshavenotchanged.Contraction:myosin’scross-bridgesbindtoactin;thecrossbridgesthenflextoslideactin.ClickheretoplaytheSarcomereShorteningFlashAnimationThethickfilamentcalledmyosinisactuallyapolymerofmyosinmolecules,eachofwhichhasaflexiblecross-bridgethatbindsATPandactin.Thecross-bridgecyclerequiresATPThemyosin-bindingsiteonactin

becomesavailable,sothe

energizedcross-bridgebinds.1.Thefull

hydrolysisanddeparture

ofADP+Pi

causesthe

flexingof

thebound

cross-bridge.2.Bindingofa“new”ATPtothecross-bridgeuncouplesthebridge.3.

PartialhydrolysisoftheboundATPenergizesor“re-cocks”thebridge.4.Themyosin-bindingsiteonactin

becomesavailable,sothe

energizedcross-bridgebinds.1.Thefull

hydrolysisanddeparture

ofADP+Pi

causesthe

flexingof

thebound

cross-bridge.2.Bindingofa“new”ATPtothecross-bridgeuncouplesthebridge.3.

PartialhydrolysisoftheboundATPenergizesor“re-cocks”thebridge.4.Thecross-bridgecyclerequiresATPThemyosin-bindingsiteonactin

becomesavailable,sothe

energizedcross-bridgebinds.1.Thefull

hydrolysisanddeparture

ofADP+Pi

causesthe

flexingof

thebound

cross-bridge.2.Bindingofa“new”ATPtothecross-bridgeuncouplesthebridge.3.

PartialhydrolysisoftheboundATPenergizesor“re-cocks”thebridge.4.ClickheretoplaytheCross-bridgecycleFlashAnimationInrelaxedskeletalmuscle,tropomyosinblocksthecross-bridgebindingsiteonactin.Contractionoccurswhencalciumionsbindtotroponin;thiscomplexthenpullstropomyosinawayfromthecross-bridgebindingsite.Rolesoftroponin,tropomyosin,andcalciumincontractionInteractionofmyosinandactinExcitation-contractioncouplingTransmissionofactionpotential(AP)alongTtubulesCalciumreleasecausedbyTtubuleAPContractioninitiatedbycalciumionsThelatentperiodbetweenexcitationanddevelopmentoftensioninaskeletalmuscleincludesthetimeneededtoreleaseCa++fromsarcoplasmicreticulum,movetropomyosin,andcyclethecross-bridges.Thetransversetubulesbringactionpotentialsintotheinterioroftheskeletalmusclefibers,sothatthewaveofdepolarizationpassesclosetothesarcoplasmicreticulum,stimulatingthereleaseofcalciumions.Theextensivemeshworkofsarcoplasmicreticulumassuresthatwhenitreleasescalciumionstheycanreadilydiffusetoallofthetroponinsites.Passageofanactionpotentialalongthetransversetubuleopensnearbyvoltage-gatedcalciumchannels,the“ryanodinereceptor,”locatedonthesarcoplasmic

reticulum,andcalciumionsreleasedintothecytosolbindtotroponin.

Thecalcium-troponincomplex“pulls”tropomyosinoffthemyosin-bindingsiteofactin,thusallowingthebindingofthecross-bridge,followedbyitsflexingto

slidetheactinfilament.GeneralprocessofexcitationandcontractioninskeletalmuscleNeuromusculartransmissionExcitation-contractioncouplingMusclecontractionAsinglemotorunitconsistsofamotorneuronandallofthemusclefibersitcontrols.Theneuromuscularjunctionisthepointofsynapticcontactbetweentheaxonterminalofamotorneuronandthemusclefiberitcontrols.Actionpotentialsinthemotorneuroncauseacetylcholinereleaseintotheneuromuscularjunction.Musclecontractionfollowsthedeliveryofacetylcholinetothemusclefiber.1.Theexocytosisofacetylcholinefromtheaxonterminaloccurswhentheacetylcholinevesiclesmergeintothemembranecoveringtheterminal.2.Onthemembraneofthemusclefiber,thereceptorsforacetylcholinerespondtoitsbindingbyincreasingNa+entryintothefiber,causingagradeddepolarization.3.Thegradeddepolarizationtypicallyexceedsthresholdforthenearbyvoltage-gateNa+andK+channels,soanactionpotentialoccursonthemusclefiber.Endplatepotential(EPP)ClickheretoplaytheNeuromuscularJunctionFlashAnimationClickheretoplaytheActionPotentialsandMuscleContractionFlashAnimationMechanicsofsingle-fibercontractionMuscletension–theforceexertedonanobjectbyacontractingmuscleLoad–theforceexertedonthemusclebyanobject(usuallyitsweight)Isometriccontraction–amuscledevelopstensionbutdoesnotshorten(orlengthen)(constantlength)Isotoniccontraction–themuscleshortenswhiletheloadonthemuscleremainsconstant(constanttension)TwitchcontractionThemechanicalresponseofasinglemusclefibertoasingleactionpotentialisknowasaTWITCHTensionincreasesrapidlyanddissipatesslowlyShorteningoccursslowly,onlyaftertakingupelastictension;therelaxingmusclequicklyreturnstoitsrestinglength.iso=sametonic=tensionmetric=lengthAllthreeareisotoniccontractions.LatentperiodVelocityofshorteningDurationofthetwitchDistanceshortenedLoad-velocityrelationClickheretoplaytheMechanismsofSingleFiberContractionFlashAnimationCompletedissipationofelastictensionbetweensubsequentstimuli.S3occurredpriortothecompletedissipationofelastictensionfromS2.S3occurredpriorto

thedissipationofANYelastictensionfromS2.Frequency-tensionrelationTemporalsummation.Unfusedtetanus:partialdissipationofelastictensionbetweensubsequentstimuli.Fusedtetanus:notimefordissipationofelastictensionbetweenrapidlyrecurringstimuli.Frequency-tensionrelationMechanismforgreatertetanictensionSuccessiveactionpotentialsresultinapersistentelevationofcytosoliccalciumconcentrationLongsarcomere:actinandmyosindonotoverlapmuch,solittletensioncanbedeveloped.Length-tensionrelationShortsarcomere:actinfilamentslackroomtoslide,solittletensioncanbedeveloped.Optimal-lengthsarcomere:lotsofactin-myosinoverlapandplentyofroomtoslide.OptimallengthClickheretoplaytheLength-TensionRelationinSkeletalMusclesFlashAnimationSkeletalmuscle’scapacitytoproduceATPviaoxidativephosphorylationisfurthersupplementedbytheavailabilityofmolecularoxygenboundtointracellularmyoglobin.Inskeletalmuscle,ATPproductionviasubstratephosphorylationissupplementedbytheavailabilityofcreatinephosphate.Inskeletalmuscle,repetitivestimulationleadstofatigue,evidentasreducedtension.Restovercomesfatigue,butfatiguewillreoccursoonerifinadequaterecoverytimepasses.TypesofskeletalmusclefibersOnthebasisofmaximalvelocitiesofshorteningFastfibers–containingmyosinwithhighATPaseactivity(typeIIfibers)Slowfibers--containingmyosinwithlowATPaseactivity(typeIfibers)OnthebasisofmajorpathwaytoformATPOxidativefibers–containingnumerousmitochondriaandhavingahighcapacityforoxidativephosphorylation,alsocontaininglargeamountsofmyoglobin(redmusclefibersGlycolyticfibers--containingfewmitochondriabutpossessingahighconcentrationofglycolyticenzymesandalargestoreofglycogen,andcontaininglittlemyoglobin(whitemusclefibers)TypesofskeletalmusclefibersSlow-oxidativefibers–combinelowmyosin-ATPaseactivitywithhighoxidativecapacityFast-oxidativefibers--combinehighmyosin-ATPaseactivitywithhighoxidativecapacityandintermediateglycolyticcapacityFast-glycolyticfibers--combinehighmyosin-ATPaseactivitywithhighglycolyticcapacitySlow-oxidativeskeletalmusclerespondswelltorepetitivestimulationwithoutbecomingfatigued;musclesofbodypostureareexamples.Fast-oxidativeskeletalmusclerespondsquicklyandtorepetitivestimulationwithoutbecomingfatigued;musclesusedinwalkingareexamples.Fast-glycolyticskeletalmuscleisusedforquickburstsofstrongactivation,suchasmusclesusedtojumportorunashortsprint.Mostskeletalmusclesincludeall

three

types.