肌細(xì)胞的收縮功能(2013)

骨骼肌SkeletalMuscle

肌纖維=肌細(xì)胞運動神經(jīng)元：其軸突支配肌纖維運動單位MotorUnit=一個運動神經(jīng)元amotorneuron+肌纖維

musclefibersCa2+

通道的開放和Ach的釋放末梢鈕扣:含有上千個囊泡，Ach存在其中。Theaxonterminalisenlargedintotheterminalbutton.EachterminalbuttoncontainsthousandsofvesiclesthatstoreAch.動作電位可觸發(fā)末梢鈕扣處的電壓門控鈣離子通道打開。鈣離子內(nèi)流可引起Ach以出胞方式釋放。PropagationofactionpotentialtheterminaltriggerstheopeningofCa2+channelsintheterminalbutton.ItpermitsCa2+todiffuseintotheterminalbuttonfromextracellularfluid,whichinturncausesthereleaseofAchbyexocytosisfromthevesicles.終板電位

Endplatepotential

Ach與運動終板上受體結(jié)合，誘導(dǎo)Na+-K+，化學(xué)門控通道開放。BindingofAchwiththereceptorsiteinthemotorend-plateinducestheopeningofchannels.鈉進(jìn)多于鉀出，使運動終板去極化，產(chǎn)生終板電位（EPP）（終板膜本身無電壓門控鈉通道，故不會產(chǎn)生動作電位）形成局部電流后可使鄰近肌膜產(chǎn)生動作電位。

MoreNa+movesinwardthanK+outward,bringingaboutadepolarizationofthemotorendplate-----Thispotentialisknownasend-platepotential(EPP).Localcurrentcanreachthethresholdofadjacentmusclefibermembrane）

andbringaboutanactionpotential.乙酰膽堿酯酶Acetylcholinesterase運動終板表面含乙酰膽堿酯酶，可分解突觸間隙游離的ACh

。Thesurfaceofthemotorendplatecontainstheenzymesacetylcholinesterase,whichcanbreakdownfreeAchinthecleft.AstheconcentrationoffreeAChfallsbecauseofitsbreakdownbyacetylcholinesterase,lessAChisavailabletobindtothereceptors.WhenreceptorsnolongercontainboundAch,theionchannelsintheendplateclose.ThedepolarizedendplatereturnstoitsrestingpotentialandcanrespondtothesubsequentarrivalofACh.有機(jī)磷農(nóng)藥中毒有機(jī)磷農(nóng)藥中毒一般認(rèn)為是抑制了膽堿酯酶的活性，造成組織中乙酰膽堿的積聚，其結(jié)果引起膽堿能受體活性紊亂，而使有膽堿能受體的器官功能發(fā)生障礙。凡由臟器平滑肌、腺體、汗腺等興奮而引起的癥狀，與毒蕈中毒所引起的癥狀相似，則稱為毒蕈樣癥狀；凡由交感神經(jīng)節(jié)和橫紋肌活動異常所引起的癥狀，與煙堿中毒所引起的癥狀相似，故稱煙堿樣癥狀。癥狀副交感神經(jīng)和分布于汗腺的交感神經(jīng)節(jié)后纖維的膽堿能受體興奮，表現(xiàn)腺體分泌增加，可見大汗、流涎和支氣管分泌物增多。虹膜括約肌收縮使瞳孔縮小，胃腸平滑肌興奮引起惡心、嘔吐、腹瀉、腹痛。心血管系統(tǒng)受抑制而致心跳緩慢，血壓下降。以上癥狀與毒蕈中毒癥狀相似故稱毒蕈堿樣

癥狀運動神經(jīng)肌肉連接點膽堿能受體興奮，表現(xiàn)肌肉纖維顫動或抽搐，晚期則見肌無力或麻痹。交感神經(jīng)節(jié)前纖維和支配腎上腺髓質(zhì)交感神經(jīng)膽堿能受體興奮可見血壓上升、心率加快、體溫升高等癥狀，這與煙堿中毒的癥狀相似，稱煙堿樣作用。中樞神經(jīng)細(xì)胞觸突間膽堿能受體興奮，則產(chǎn)生中樞神經(jīng)系統(tǒng)功能失調(diào)癥狀，中毒早期有頭暈、頭痛以后出現(xiàn)言語障礙、神志不清和陣發(fā)性抽搐等，有機(jī)磷中毒可因呼吸中樞麻痹而致死。治療洗胃：可用2%～4%碳酸氫鈉溶液洗胃，也可用生理鹽水或清水洗胃膽堿能神經(jīng)抑制劑：如阿托品可拮抗乙酰膽堿的毒蕈堿樣作用。膽堿酯酶復(fù)活劑：有解磷定氯解磷定、雙復(fù)磷等，它們可奪取與膽堿酯酶結(jié)合的有機(jī)磷，恢復(fù)膽堿酯酶分解乙酰膽堿的活力。

神經(jīng)-肌接頭傳遞各環(huán)節(jié)

Actionpotentialinpresynapticnerveterminal

depolarization

Ca2+channelsopen

intracellularCa2+

acetylcholinevesiclereleaseACh

synapticcleft

bindstopostsynapticAChreceptor

postsynapticmembranedepolarization

end-platepotential(EPP)

actionpotentialinmusclecelloccurs

contractionofmusclecell.箭毒傳說美洲的古印第安人在遇到敵人入侵時，女人和兒童在后方將箭毒木的汁液涂于箭頭，供男人在戰(zhàn)場上殺敵。1859年土著民族在和英軍交戰(zhàn)時，這種毒箭的殺傷力使英軍驚恐萬分。傳說西雙版納最早發(fā)現(xiàn)箭毒木汁液含有劇毒的是一位傣族獵人。這位獵人被一只碩大的狗熊緊逼而被迫爬上一棵大樹，可狗熊仍不放過他,生死存亡的緊要關(guān)頭，獵人折斷一根樹枝刺向正往樹上爬的狗熊，奇跡突然發(fā)生了，狗熊立即落地而死。從那以后獵人就學(xué)會了把箭毒木的汁液涂于箭頭用于狩獵。

又稱見血封喉樹“七上八下九倒地”，意思就是說，如果誰中了箭毒木的毒，那么往高處只能走七步，往低處只能走八步，但無論如何，走到第九步，都會倒地斃命箭毒木又名加獨樹、剪刀樹等高可達(dá)30米，多分布于赤道熱帶地區(qū)，國內(nèi)則散見于廣東、廣西、海南、云南等省區(qū)?，F(xiàn)為瀕臨滅絕的稀有樹種，國家三級保護(hù)植物。南美箭毒Curare

ThedeadlySouthAmericanarrowheadpoisoncurarebindsstronglytotheAChreceptors,butitdoesnotopentheirionchannelsandisnotdestroyedbyacetylcholinesterase.Whenareceptorisoccupiedbycurare,AChcannotbindtothereceptor.Hence,thereisnoEPPinthemotorendplateandnocontraction.Sincetheskeletalmusclesresponsibleforbreathing（呼吸）,curarepoisoningcanleadtodeathbyasphyxiation（窒息）.肉毒桿菌毒素BotulinandAChBotulinisanenzymethatbreaksdownaproteinrequiredforthebindingandfusionofACh

vesecleswiththepresynapticmembrane.

Hence,itcanblockthereleaseofacetylcholinefromnerveterminals

inneuromuscularjunction.Thispoisoningisoneofthemostpotentpoisons,whichcancauseflaccidparalysis（肌肉松馳性癱瘓）.生物武器

它造價低，技術(shù)難度不大，隱秘性強(qiáng)，可以在任何地方研制和生產(chǎn)。有資料顯示，以1969年為例，當(dāng)時每平方公里導(dǎo)致50%死亡率的成本分別為：傳統(tǒng)武器2000美元；核武器，800美元；化學(xué)武器，600美元；生物武器，1美元。

肉毒桿菌毒素----“窮人的原子彈”肉毒桿菌毒素是最流行的兩大生物武器之一,是一種廉價和高效的殺人武器，其死亡率高達(dá)60%至70%。受害者癥狀是頭痛、肢體癱瘓，如不及時治療將在2至10天內(nèi)死去。這種毒素可以批量生產(chǎn)，并可通過皮膚吸收、肺部吸收、眼睛接觸、等方式傳染。肉毒桿菌毒素----“富人的美容劑”肉毒桿菌毒素除皺紋的原理很簡單，A型肉毒毒素可以起到麻痹肌肉的作用，臉部注射后，阻斷神經(jīng)和肌肉之間的信息傳導(dǎo)，可使局部肌肉癱瘓，肌膚因此舒展，皺紋便神奇般消失A型肉毒毒素注射過量可致人死命。但美容除皺注射的A型肉毒毒素是人致死量的3%。注入肌肉后它選擇性使肌肉松弛，幾乎無多余的A型肉毒毒素進(jìn)入血液或進(jìn)入人腦脊液。骨骼肌的構(gòu)成

Organizationofskeletalmuscle骨骼肌是由肌纖維組成。Skeletalmuscleismadeofindividualmusclefibers.肌纖維是由肌原纖維組成。Themusclefibersaremadeofmyofibrils.肌原纖維由肌絲構(gòu)成。Thefibrilsaredividedintoindividualfilaments.肌絲由收縮蛋白構(gòu)成。Thefilamentsaremadeupofthecontractileproteins.肌絲Filaments肌原纖維：含有粗肌絲和細(xì)肌絲

Themyofibrilscontainthickandthinfilamentscomposedofcontractileproteins.粗肌絲：含有肌凝蛋白，又稱肌球蛋白。Thickfilamentscontaintheproteinmyosin.細(xì)肌絲：含有肌纖蛋白（又稱肌動蛋白）、原肌凝蛋白（原肌球蛋白）和肌鈣蛋白。

Thinfilamentscontainproteinsactin,tropomyosin,andtroponin.橫管TTubule與肌漿網(wǎng)SR

之間的關(guān)系TransverseTubule（Ttubule橫管）isformedasaninvagination

（凹入）ofthesurfaceofthemusclemembrane.TheactionpotentialspreadingoverthesurfaceofthemusclemembraneispropagatedintothenetworkofTtubules,whichformscontactswithsarcoplasmicreticulum(SR肌漿網(wǎng))SRcontainsahighconcentrationofCa2+,

肌漿網(wǎng)（SR）和

Ca2+釋放T管含有二氫吡啶受體,屬電壓敏感受體，又稱L-型Ca2+

通道。局部去極化可激活該受體，進(jìn)而使終末池上的鈣離子釋放通道開放。TheTtubulemembranecontainsdihydropyridinereceptor(WhenanactionpotentialispropagateddowntheTtubule,thelocaldepolarizationactivatesdihydrpopyridine

recepotorthatinturnopenstheCa2+releasechannelalsoknownasryanodinereceptor)onSR.肌鈣蛋白及其作用由三個亞單位組成：肌鈣蛋白T（TnT)、肌鈣蛋白I(TnI)和肌鈣蛋白C(TnC)TnT與原肌凝蛋白結(jié)合，將整個肌鈣蛋白固定在原肌凝蛋白上。TnC可與Ca++結(jié)合。TnI的作用是TnC可與Ca++結(jié)合時，將信息傳給原肌凝蛋白，引起后者發(fā)生構(gòu)象變化并向肌纖蛋白雙螺旋溝深部滑行，從而暴露肌纖蛋白的結(jié)合位點，使橫橋與之結(jié)合。粗肌絲、橫橋與細(xì)肌絲的關(guān)系Pullingthinfilamentsinwardbythebendofcrossbridgesisdirectedtowardthecenterofthethickfilament.Eachthickfilamentissurroundedbysixthinfilaments,allthewhicharepulledinwardsimultaneouslythroughcross-bridgecyclingduringmusclecontraction.從神經(jīng)元動作電位到肌纖維收縮-----(1)1.Actionpotentialisinitiatedandpropagatesinmotorneuronaxon.2.ActionpotentialtriggersreleaseofAchfromaxonterminalsatneuromuscularjunctions.3.Achbindstoreceptorsitesonmotorendplateinmusclefiber,openingNa+,K+ionchannel.從神經(jīng)元動作電位到肌纖維收縮-----(2)4.MoreNa+movesintothefiberatthemotorendplatethanK+moveout,depolarizingthemembrane,producingtheend-platepotential(EPP).5.Localcurrentsdepolarizetheadjacentplasmamembranetoitsthresholdpotential,generatinganactionpotentialthatpropagatesoverthemusclefibersurfaceandintothefiberalongTtubles.從神經(jīng)元動作電位到肌纖維收縮-----(3)6.ActionpotentialinTtubulestriggersreleaseofCa2+fromlateralsacsofSR.7.Ca2+bindstotroponin（肌鈣蛋白）

onthinfilaments,causingtropomyosin（原肌球蛋白）

tomoveawayfromitsblockingpositionandthusuncoveringcross-bridgesbindingsitesonactin（肌纖蛋白）.從神經(jīng)元動作電位到肌纖維收縮-----(4)8.Energizedmyosincross-bridges

（高能肌球蛋白橫橋）onthethickfilamentsbindtoactin（肌纖蛋白）.（橫橋之所以處于高勢能狀態(tài),是因其頭部具有ATP酶活,并可將與其結(jié)合ATP分解成ADP和無機(jī)磷酸而貯能.）9.Cross-bridgebindingtriggersreleaseofenergystoredinmyosin（肌球蛋白）,producingamovementofeachcrossbridge.此時ADP和無機(jī)磷酸便與橫橋分離10.在ADT分離點，ATPbindstomyosin（肌凝蛋白）,breakinglinkagebetweenactin（肌纖蛋白）andmyosinandtherebyallowingcrossbridgestodissociatefromactin.(橫橋頭部與ATP結(jié)合后，其對肌纖蛋白的親和力降低，使其與纖動蛋白解離）。11.ATPboundtomyosinissplitbymyosinATPase,transferringenergytomyosincrossbridgeonceagain.（結(jié)合到橫橋頭部的ATP被ATP酶分解，又把能量貯存在橫橋）從神經(jīng)元動作電位到肌纖維收縮-----(5)從神經(jīng)元動作電位到肌纖維收縮-----(6)12.Crossbridgesrepeatsteps8to11,producingmovementofthinfilamentspastthickfilaments.Cyclesofcross-bridgemovementcontinueaslongasCa2+remainsboundtotroponin（肌鈣蛋白）.

RelaxedstateofthemuscleThenormalconcentrationofCa2+inthecytosolthatbathesthemyofibrils（肌原纖維）

istoolittletoelicitcontraction.Therefore,intherestingstate,thetroponin-tropomyosincomplexkeepstheactinfilamentsinhibitedandmaintainsarelaxedstateofthemuscle.FunctionofATP

1.HydrolysisofATPbymyosinenergizesthecrossbridges,providingenergyforforcegeneration.2.Dissociatescrossbridgesboundtoactin.3.ProvidestheenergyfortheactivetransportofCa2+intolateralsacsofreticulum,loweringcytosolicCa2+.鈣瞬變與肌肉的收縮與舒張動作電位在引起肌細(xì)胞收縮和舒張前，引起胞質(zhì)中游離鈣濃度的上升和下降。胞質(zhì)中發(fā)生這種鈣的波動，稱為鈣瞬變。鈣瞬變上升速度快，肌細(xì)胞縮短速度快；鈣瞬變幅度大，肌細(xì)胞縮短幅度大。鈣瞬變下降速度慢，肌細(xì)胞舒張變慢。肌肉收的形式和力學(xué)分析Isometriccontraction（等長收縮）:Whenamuscledevelopstensionbutdoesnotshorten.(長度不變,張力增加)Isotoniccontraction（等張收縮）:Whenamuscleisshorteningbutitstensionremainsconstant.(長度縮短,張力不變)等張收縮舉例

Anexampleofisotoniccontraction手臂可以提起一個物體時的狀態(tài)Liftinganobject:Whenthetensiondevelopinginyourbicepsbecomesgreatenoughtoovercometheweightoftheobjectinyourhand,youcanlifttheobject,withthewholemuscleshortening.Becausetheweightoftheobjectdoesnotchangeasitislifted,themuscletensionremainsconstantthroughouttheperiodofshortening.Thisisisotoniccontraction.等長收縮舉例

Anexampleofisometriccontraction

想提起一重物,但太重提不起時的狀態(tài)Trytoliftanobject:Whathappensifyoutrytoliftanobjecttooheavyforyou,thatis,ifthetensionyouarecapableofdevelopinginyourarmmusclesislessthanthatrequiredtolifttheobject?Themusclecannotshortenandlifttheobjectbutremainsatconstantlengthinspiteofthedevelopmentoftension.Thisisanisometriccontraction前負(fù)荷

Preloadand

后負(fù)荷

Afterload前負(fù)荷:

肌肉在收縮前就加上肌肉上的負(fù)荷.

Theforcerequiredtostretchthemuscletolengthsbeyond2.0m).后負(fù)荷:

肌肉開始收縮后遇到的負(fù)荷.Theweightthatamuscleliftsduringanisotoniccontraction).最適長度Optimallength最適長度:Thelengthatwhichthemusclefiberdevelopsthegreatesttension.Ataninitialsarcomerelength（肌小節(jié)長度）

of2.2um,eachcross-bridgecanbindtoanactinmoleculeonthinfilaments,andamaximumforceisgenerated.

長度與張力的關(guān)系

Length-tensionrelationship

Maximaltetaniccontractioncanbeachievedwhenamusclefiberisatitsoptimallength.Whenitislonger,fewerthin-filamentbindingsitesareaccessibleforbindingwiththick-filamentcrossbridges,becausethethinfilamentsarepulledout.Whenthefiberisshorter,fewerthin-filamentbindingsitesareexposedtothick-filamentcrossbridgesbecausethethinfilamentsoverlap.體內(nèi)長度與張力的關(guān)系

Length-tensionrelationshipinthebody

Inthebody,themusclerelaxedlengthisapproximatelytheiroptimallength,thus,themusclearecapableofachievingnear-maximaltetaniccontractionmostofthetime.Becauseoflimitationsimposedbyattachmenttotheskeleton,amusclecannotbestretchedorshortenedmorethan30%ofitsrestingoptimallength,evenattheouterlimits(130%and70%ofoptimallength),themusclearestillabletogeneratehalftheirmaximaltension.

負(fù)荷與速度的關(guān)系

Load-velocityrelationship

Thegreatertheload,thelowerthevelocityatwhichasinglemusclefibershortensduringanisotoniccontraction.Thevelocityofshorteningismaximalwhenthereisnoexternalload.Thevelocityofshorteningprogressivelydecreaseswithanincreasingload,andfallstozerowhenloadcannotbeovercomebymaximaltension.頻率與張力的關(guān)系

Frequencyandtensionrelation潛伏期Latentperiod:Followingtheactionpotential,thereisaintervalofafewmillisecondsbeforethetensioninmusclefiberbeginstoincrease(theprocessesassociatedwithexcitation-contractioncoupling)單收縮Singletwitch:Amechanicalresponseofamusclefibertoasingleactionpotential

頻率與張力的關(guān)系

Frequencyandtensionrelation

強(qiáng)直收縮Tetanus