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ElectrophysiologyofMuscleSkeletal&Cardiacexcitation&contractionMikeClark,M.D.NOTEPriortoreadingthisPowerPointpresentation–studentsmaywanttoreviewmyPowerPointpresentationGeneralElectrophysiology–whichexplainstheRestingMembranePotentialandActionPotentialsingeneral.NeuronActionPotentialSkeletalMuscleActionPotentialEventsinNeuronActionPotential1.Athresholdvoltagethereisimmediateopeningofthesodiumvoltagedependentactivationgate2.AtthresholdthereisthestartofslowclosureofthesodiumvoltagedependentinactivationgateResultfromtheabovetwoeventssodiumcanrushintotheneuronbecausebothgatesaretemporarilyopentosodiumAsaresultofthepositivesodiumionsrushinginthroughtheopengatesyougetstep2depolarizationofthemembrane3.Whentheslowsodiuminactivationgateclosesthepositivesodiumionsstoprushinginandthemembranedepolarizesnofurther–theup-shootstops.4.Thesamevoltagethatoperatedthesodiumgatesalsoisthesamevoltagetoinitiateactionofthepotassiumgates–howeverthepotassiumgatesareveryslowsotheydonotopentillaroundthetimethatthesodiuminactivationgateisclosing–thussincenofurthersodiumisrushingInandnowpositivepotassiumisrushingouttheinsideoftheneuronagainbeginstobecomeMorenegative–Repolarization.5.Justlikethepotassiumgatewasslowtoopenitisalsoslowtoclose–thusanovershootofpotassiummovesoutofthecell–causingtheinterioroftheneurontobecomemorenegativethanatthestart(RestingMembranePotential).Thisovershootistermed“hyperpolarization.”6.TheneuronmustagainreturntotheRestingMembranePotentialstate–thisisaresultoftheSodium/Potassiumpump(3Naoutfor2Kin)actionandthelargeintracellularmolecularanions(discussedintheGeneralelectrophysiologyPowerPoint).RefractoryPeriods•AbsoluteRefractoryPeriod–atimeinwhichthesameareaoftheneuroncellmembranecannotbere-excited(fireanotheractionpotential).Itistimeittakesforthesodiumgatestofullyreset.•RelativeRefractoryPeriod–atimeimmediatelyaftertheabsoluterefractoryperiodinwhichthesameareaoftheneuroncellmembranecanbere-excitedbutrequiresahighervoltagehigherthantheusualthresholdvoltage.Duringthistimethepotassiumchannelsarestillopen–thuspositivepotassiumisrushingoutmakingtheinterioroftheneuronmorenegativethushardertoreachthevoltageofthreshold.EventsinaSkeletalMuscleActionPotential1.Unlikeneurons–theskeletalmusclehasonlyonetypevoltagedependentsodiumgate.Whenthresholdvoltageisreacheditquicklyopensandsodiumrushesincausingthedepolarization.2.Thesodiumvoltagedependentgatelaterclosesanddepolarizationstops.3.Thesamevoltage(Thresholdvoltage)thatcausestheopeningoftheNagatesisthesameVoltagethatopensthepotassiumgatesbuttheyareslower-openingaboutthesametimethattheNagatesareClosing–KrushesoutcausingRepolarization•Na/KpumpandlargermolecularanionsReturnmembranetoRestingState(RMP)Excitation-ContractionCoupling•Neuronscanillicitconductivity(sometimesreferredtoasexcitation)•Thisconductivityisintheformofactionpotentials•Musclecanillicitthechargeactivityofconductivityaswellasthemechanicalactivityofcontractility•Thechargemovementofconductivity(actionpotentials)leadstothemechanicalcontraction–thustheexcitationmustbecoupledtothecontraction•Sincechargeactivityisfasterthanmechanicalactivity–theactionpotentialsinitiatefirstfollowedfairlyquicklybytheinitiationofthemechanicalactivityofcontraction.LatentPhaseofContractionThedifferentialintimebetweenwhentheactionpotentialsinitiateandthecontractioninitiatesistermedthelatentphaseofmusclecontractionActionpotentialinitiatedLatentPhaseThelatentphaseinvolvesalltheeventsaftertheactionpotentialtillthemyosindragstheactinoverit(slidingfilament)–thuscausingtheinitiationofthemusclecontractionActualContraction(skeletalmuscle)Thoughtheactionpotentialonlylasts1to3millisecondstheskeletalmusclecontractionlastsover100msAcontractionasaresultofoneactionpotentialistermedamuscletwitch.Amuscletwitchhas3periods–latent,contractionandrelaxation.100millisecondsis1/10ofasecond•100milliseconds(1/10thofasecond)isnotalongtimeatall–wecouldnotdoanythingmusclewiseinthattimeframe–thuswemustadd(summate)togethertheseisolatedcontractions(muscletwitch)–tomakealongerusefulcontraction.Theaddingtogetherofmuscletwitchesistermed“tetany.”•Tetanyoccursbydeliveringtothemusclecell-arapidcontinuoussetofactionpotentials.•Theactionpotentialscanoccurfastbuthowclosetogethertheycanoccurislimitedbytheactionpotentials“absoluterefractoryperiod.”TetanyActionpotentialsbeingdeliveredinrapidsuccession–thusmaintainingasustainedskeletalmusclecontraction.Theeventscausingheartmusclecontractiondifferslightlyfromthoseofskeletalmuscle•Cardiacmuscle–justasskeletalmuscle-requirecalciumtoallowactintobindtomyosin–whichisthemaincomponentoftheslidingfilamentmodelofmusclecontraction.•Allthecalciumrequiredforskeletalmusclecontractionislocatedontheinsideoftheskeletalmusclecellinthesarcoplasmicreticulum–howevercardiacmusclerequiressomecalciumtoenterfromoutsideofthemusclecell.•incardiacmusclesome(10-20%)extracellularcalciumisrequiredforcontraction.ThiscalciumentersthroughvoltagedependentcalciumchannelsknownasLchannelsorsometimesreferredtoasslowcalciumchannels.releaseInfactthe10-20%ofcalciumcomingfrom