musclecell肌细胞-17年-2011年.ppt

骨骼肌SkeletalMuscle Asingleskeletal musclecellisknownasamusclefiber 肌纤维 Thenervecellswhoseaxons 轴突 innervate 支配 skeletalmusclefibersareknownasmotorneurons 运动神经元 运动单位MotorUnit amotorneuron musclefibers 神经肌接头的传递Nuromusculartransmission Thealphamotoneuronbranches asitapprochesthemuscle sendingaxonterminals 轴突末梢 toseveralskeletalmusclefibers Synaptictransmission 突触传递 occursattheend plateregion 终板区 i e thepostsynapticmembranes突触后膜 oftheskeletalmusclefiber Ca2 通道的开放和Ach的释放 Theaxonterminalisenlargedintotheterminalbutton 末梢钮扣 EachterminalbuttoncontainsthousandsofvesiclesthatstoreAch PropagationofactionpotentialtheterminaltriggerstheopeningofCa2 channelsintheterminalbutton ItpermitsCa2 todiffuseintotheterminalbuttonfromextracellularfluid whichinturncausesthereleaseofAchbyexocytosis 出胞 fromthevesicles 终板电位Endplatepotential BindingofAchwiththereceptorsiteinthemotorend plateinducestheopeningofchannels bothNa andK 为化学门控通道 MoreNa movesinwardthanK outward bringingaboutadepolarizationofthemotorendplate Thispotentialisknownasend platepotential EPP 终板膜本身无电压门控钠通道 故不会产生动作电位 但可形成局部电流 Localcurrentcanreachthethresholdofadjacentmusclefibermembrane 邻近肌膜 andbringaboutanactionpotential 乙酰胆碱酯酶Acetylcholinesterase Thesurfaceofthemotorendplatecontainstheenzymesacetylcholinesterase whichcanbreakdown 分解 freeAchinthecleft AstheconcentrationoffreeAChfallsbecauseofitsbreakdownbyacetylcholinesterase lessAChisavailabletobindtothereceptors WhenreceptorsnolongercontainboundAch theionchannelsintheendplateclose ThedepolarizedendplatereturnstoitsrestingpotentialandcanrespondtothesubsequentarrivalofACh 神经 肌接头传递各环节 Actionpotentialinpresynapticnerveterminal depolarization Ca2 channelsopen intracellularCa2 acetylcholinevesiclereleaseACh synapticcleft bindstopostsynapticAChreceptor postsynapticmembranedepolarization end platepotential EPP actionpotentialinmusclecelloccurs contractionofmusclecell 箭毒传说 美洲的古印第安人在遇到敌人入侵时 女人和儿童在后方将箭毒木的汁液涂于箭头 供男人在战场上杀敌 1859年土著民族在和英军交战时 这种毒箭的杀伤力使英军惊恐万分 传说西双版纳最早发现箭毒木汁液含有剧毒的是一位傣族猎人 这位猎人被一只硕大的狗熊紧逼而被迫爬上一棵大树 可狗熊仍不放过他 生死存亡的紧要关头 猎人折断一根树枝刺向正往树上爬的狗熊 奇迹突然发生了 狗熊立即落地而死 从那以后猎人就学会了把箭毒木的汁液涂于箭头用于狩猎 又称见血封喉树 七上八下九倒地 意思就是说 如果谁中了箭毒木的毒 那么往高处只能走七步 往低处只能走八步 但无论如何 走到第九步 都会倒地毙命 箭毒木又名加独树 剪刀树等 高可达30米 多分布于赤道热带地区 国内则散见于广东 广西 海南 云南等省区 现为濒临灭绝的稀有树种 国家三级保护植物 南美箭毒Curare ThedeadlySouthAmericanarrowheadpoisoncurarebindsstronglytotheAChreceptors butitdoesnotopentheirionchannelsandisnotdestroyedbyacetylcholinesterase Whenareceptorisoccupiedbycurare AChcannotbindtothereceptor Hence thereisnoEPPinthemotorendplateandnocontraction Sincetheskeletalmusclesresponsibleforbreathing 呼吸 curarepoisoningcanleadtodeathbyasphyxiation 窒息 肉毒杆菌毒素BotulinandACh BotulinisanenzymethatbreaksdownaproteinrequiredforthebindingandfusionofAChvesecleswiththepresynapticmembrane Hence itcanblockthereleaseofacetylcholinefromnerveterminalsinneuromuscularjunction Thispoisoningisoneofthemostpotentpoisons whichcancauseflaccidparalysis 肌肉松驰性瘫痪 生物武器 它造价低 技术难度不大 隐秘性强 可以在任何地方研制和生产 有资料显示 以1969年为例 当时每平方公里导致50 死亡率的成本分别为 传统武器2000美元 核武器 800美元 化学武器 600美元 生物武器 1美元 肉毒杆菌毒素 穷人的原子弹 肉毒杆菌毒素是最流行的两大生物武器之一 是一种廉价和高效的杀人武器 其死亡率高达60 至70 受害者症状是头痛 肢体瘫痪 如不及时治疗将在2至10天内死去 这种毒素可以批量生产 并可通过皮肤吸收 肺部吸收 眼睛接触 等方式传染 肉毒杆菌毒素 富人的美容剂 肉毒杆菌毒素除皱纹的原理很简单 A型肉毒毒素可以起到麻痹肌肉的作用 脸部注射后 阻断神经和肌肉之间的信息传导 可使局部肌肉瘫痪 肌肤因此舒展 皱纹便神奇般消失A型肉毒毒素注射过量可致人死命 但美容除皱注射的A型肉毒毒素是人致死量的3 注入肌肉后它选择性使肌肉松弛 几乎无多余的A型肉毒毒素进入血液或进入人脑脊液 有机磷Organophosphatesandacetylcholinerase Someorganophosphates whicharethemainingredientsincertainpesticides 农药 and nervegases inhibitacetylcholinesterase WhenAChbindstotheendplatereceptors whichisnotdestroyed producingamaintaineddepolarizationintheendplateandmuscleplasmamembrane Hence sodiumchannelsenteraninactivestate Muscledoesnotcontractinresponsetosubsequentnervestimulation andresultisdeathfromasphyxiation 窒息 Organizationofskeletalmuscle Skeletalmuscleismadeofindividualmusclefibers 肌纤维 Themusclefibersaremadeoffibrils 肌原纤维 Thefibrilsaredividedintoindividualfilaments 肌丝 Thefilamentsaremadeupofthecontractileproteins 收缩蛋白 肌丝Filaments Themyofibrils 肌原纤维 containthick 粗肌丝 andthinfilaments 细肌丝 composedofcontractileproteins 粗肌丝Thickfilamentscontaintheproteinmyosin 肌球蛋白 含有横桥 Thinfilamentscontainproteinsactin 肌动蛋白 tropomyosin 原肌球蛋白 andtroponin 肌钙蛋白 横管TTubule与肌浆网SR之间的关系 TransverseTubule Ttubule横管 isformedasaninvagination 凹入 ofthesurfaceofthemusclemembrane TheactionpotentialspreadingoverthesurfaceofthemusclemembraneispropagatedintothenetworkofTtubules whichformscontactswithsarcoplasmicreticulum SR肌浆网 SRcontainsahighconcentrationofCa2 肌质网SRandCa2 release TheTtubulemembranecontainsdihydropyridinereceptor 二氢吡啶受体 avoltage sensitivereceptor电压敏感受体 L 型Ca2 通道 WhenanactionpotentialispropagateddowntheTtubule thelocaldepolarizationactivatesdihydrpopyridinerecepotorthatinturnopenstheCa2 releasechannel 终池上的钙离子释放通道 alsoknownasryanodinereceptor onSR 肌钙蛋白及其作用 由三个亚单位组成 肌钙蛋白T TnT 肌钙蛋白I TnI 和肌钙蛋白C TnC TnT与原肌球蛋白结合 将整个肌钙蛋白固定在原肌球蛋白上 TnC可与Ca 结合 TnI的作用是TnC可与Ca 结合时 将信息传给原肌球蛋白 引起后者发生构象变化并向肌纤蛋白双螺旋沟深部滑行 从而暴露肌纤蛋白的结合位点 使横桥与之结合 粗肌丝 横桥与细肌丝的关系 Pullingthinfilamentsinwardbythebendofcrossbridgesisdirectedtowardthecenterofthethickfilament Eachthickfilamentissurroundedbysixthinfilaments allthewhicharepulledinwardsimultaneouslythroughcross bridgecyclingduringmusclecontraction 从神经元动作电位到肌纤维收缩 1 1 Actionpotentialisinitiatedandpropagatesinmotorneuronaxon 2 ActionpotentialtriggersreleaseofAchfromaxonterminalsatneuromuscularjunctions 3 Achbindstoreceptorsitesonmotorendplateinmusclefiber openingNa K ionchannel 从神经元动作电位到肌纤维收缩 2 4 MoreNa movesintothefiberatthemotorendplatethanK moveout depolarizingthemembrane producingtheend platepotential EPP 5 Localcurrentsdepolarizetheadjacentplasmamembranetoitsthresholdpotential generatinganactionpotentialthatpropagatesoverthemusclefibersurfaceandintothefiberalongTtubles 从神经元动作电位到肌纤维收缩 3 6 ActionpotentialinTtubulestriggersreleaseofCa2 fromlateralsacsofSR 7 Ca2 bindstotroponin 肌钙蛋白 onthinfilaments causingtropomyosin 原肌球蛋白 tomoveawayfromitsblockingpositionandthusuncoveringcross bridgesbindingsitesonactin 肌纤蛋白 从神经元动作电位到肌纤维收缩 4 8 Energizedmyosincross bridges 高能肌球蛋白横桥 onthethickfilamentsbindtoactin 肌纤蛋白 横桥之所以处于高势能状态 是因其头部具有ATP酶活 并可将与其结合ATP分解成ADP和无机磷酸而贮能 9 Cross bridgebindingtriggersreleaseofenergystoredinmyosin 肌球蛋白 producingamovementofeachcrossbridge 此时ADP和无机磷酸便与横桥分离 10 在ADT分离点 ATPbindstomyosin 肌凝蛋白 breakinglinkagebetweenactin 肌纤蛋白 andmyosinandtherebyallowingcrossbridgestodissociatefromactin 横桥头部与ATP结合后 其对肌纤蛋白的亲和力降低 使其与纤动蛋白解离 11 ATPboundtomyosinissplitbymyosinATPase transferringenergytomyosincrossbridgeonceagain 结合到横桥头部的ATP被ATP酶分解 又把能量贮存在横桥 从神经元动作电位到肌纤维收缩 5 从神经元动作电位到肌纤维收缩 6 12 Crossbridgesrepeatsteps8to11 producingmovementofthinfilamentspastthickfilaments Cyclesofcross bridgemovementcontinueaslongasCa2 remainsboundtotroponin 肌钙蛋白 Relaxedstateofthemuscle ThenormalconcentrationofCa2 inthecytosolthatbathesthemyofibrils 肌原纤维 istoolittletoelicitcontraction Therefore intherestingstate thetroponin tropomyosincomplexkeepstheactinfilamentsinhibitedandmaintainsarelaxedstateofthemuscle FunctionofATP 1 HydrolysisofATPbymyosinenergizesthecrossbridges providingenergyforforcegeneration 2 Dissociatescrossbridgesboundtoactin 3 ProvidestheenergyfortheactivetransportofCa2 intolateralsacsofreticulum loweringcytosolicCa2 肌肉收的形式和力学分析 Isometriccontraction 等长收缩 Whenamuscledevelopstensionbutdoesnotshorten 长度不变 张力增加 Isotoniccontraction 等张收缩 Whenamuscleisshorteningbutitstensionremainsconstant 长度缩短 张力不变 等张收缩举例Anexampleofisotoniccontraction 手臂可以提起一个物体时的状态Liftinganobject Whenthetensiondevelopinginyourbicepsbecomesgreatenoughtoovercometheweightoftheobjectinyourhand youcanlifttheobject withthewholemuscleshortening Becausetheweightoftheobjectdoesnotchangeasitislifted themuscletensionremainsconstantthroughouttheperiodofshortening Thisisisotoniccontraction 等长收缩举例Anexampleofisometriccontraction 想提起一重物 但太重提不起时的状态Trytoliftanobject Whathappensifyoutrytoliftanobjecttooheavyforyou thatis ifthetensionyouarecapableofdevelopinginyourarmmusclesislessthanthatrequiredtolifttheobject Themusclecannotshortenandlifttheobjectbutremainsatconstantlengthinspiteofthedevelopmentoftension Thisisanisometriccontraction 前负荷Preloadand后负荷Afterload 前负荷 肌肉在收缩前就加上肌肉上的负荷 Theforcerequiredtostretchthemuscletolengthsbeyond2 0 m 后负荷 肌肉开始收缩后遇到的负荷 Theweightthatamuscleliftsduringanisotoniccontraction 最适长度Optimallength 最适长度 Thelengthatwhichthemusclefiberdevelopsthegreatesttension Ataninitialsarcomerelength 肌小节长度 of2 2um eachcross bridgecanbindtoanactinmoleculeonthinfilaments andamaximumforceisgenerated 长度与张力的关系Length tensionrelationship Maximaltetaniccontractioncanbeachievedwhenamusclefiberisatitsoptimallength Whenitislonger fewerthin filamentbindingsitesareaccessibleforbindingwiththick filamentcrossbridges becausethethinfilamentsarepulledout Whenthefiberisshorter fewerthin filamentbindingsitesareexposedtothick filamentcrossbridgesbecausethethinfilamentsoverlap 体内长度与张力的关系Length tensionrelationshipinthebody Inthebody themusclerelaxedlengthisapproximatelytheiroptimallength thus themusclearecapableofachievingnear maximaltetaniccontractionmostofthetime Becauseoflimitationsimposedbyattachmenttotheskeleton amusclecannotbestretchedorshortenedmorethan30 ofitsrestingoptimallength evenattheouterlimits 130 and70 ofoptimallength themusclearestillabletogeneratehalftheirmaximaltension 负荷与速度的关系Load velocityrelationship Thegreatertheload thelowerthevelocityatwhichasinglemusclefibershortensduringanisotoniccontraction Thevelocityofshorteningismaximalwhenthereisnoexternalload Thevelocityofshorteningprogressivelydecreaseswithanincreasingload andfallstozerowhenloadcannotbeovercomebymaximaltension 频率与张力的关系Frequencyandtensionrelation 潜伏期Latentperiod Followingtheactionpotential thereisaintervalofafewmillisecondsbeforethetensioninmusclefiberbeginstoincrease theprocessesassociatedwithexcitation contractioncoupling 单收缩Singletwitch Amechanicalresponseofamusclefibertoasi