1、神經(jīng)肌肉傳導(dǎo)電生理神經(jīng)肌肉傳導(dǎo)電生理Acetylcholinecurare是一種取自熱帶植物的劇毒藥物，被南美的土著獵人用作制作毒箭的材料curareAcetylcholineBernard 認(rèn)為 Curare 的作用位點(diǎn)是神經(jīng)與肌肉相接觸的區(qū)域（） John Langley 發(fā)現(xiàn)Nicotine 能刺激蛙的離體骨骼肌的收縮，但Curare 會(huì)使Nicotine 失效1906 John Langley 提出化學(xué)遞質(zhì)假說1921 Loewi 發(fā)現(xiàn)化學(xué)遞質(zhì)AchAcetylcholine神經(jīng)-肌接頭NMJ (neuromuscular junction)運(yùn)動(dòng)區(qū)皮質(zhì)運(yùn)動(dòng)區(qū)皮質(zhì)皮質(zhì)脊髓纖維皮質(zhì)脊髓纖維

2、皮質(zhì)脊髓束皮質(zhì)脊髓束脊髓前角運(yùn)動(dòng)神經(jīng)元脊髓前角運(yùn)動(dòng)神經(jīng)元突觸連接突觸連接NMJNMJ 骨骼肌骨骼肌nAchRArthur KarlinnAchR是一個(gè)五聚體亞基 2個(gè)、 亞基各一個(gè)或亞基nAchRAChAlphaAlphaEpsilon / GammaDeltaBetaIon ChannelAChIn fetal & denervated receptors: Gamma replaces EpsilonnAchR nAchRImmatureSpreadUnstable life 24 hrsLonger burst durationSmaller conductance2-10 ti

3、mes longer channel opening (slow closing)MatureLocalizedStable life 2 weeksBurst activity Normal conductanceChannel opens for 0.5 millisecondnAchR10 % receptors must be open for muscle action potential generation70 % receptors can be occupied before fade is observed95 % receptor occupancy required f

4、or complete twitch suppressionNMJ突觸機(jī)制突觸機(jī)制 NMJ突觸機(jī)制突觸機(jī)制K+Na+Ca2+NMJ突觸機(jī)制突觸機(jī)制Ca+K+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+Na+K+K+K+K+K+K+K+K+K+K+K+AChAChAChAChNa+Na+K+Muscle membraneNerveterminalCa2+Ca2+EPP & APMuscle membranePresynapticterminalMuscle MembraneVoltage (mV)Time (msec)-90 mVVKVNa0ThresholdPre

5、synaptic APEPPACh Receptor ChannelsVoltage-gatedNa ChannelsInward RectifierK ChannelsMeanwhile .AChACh unbinds fromits receptorMuscle membraneAChso the channel closesAChAChNerveterminalACh is hydrolyzed byAChE into Cholineand acetateCholineAcetateCholine is taken upinto nerve terminalCholineCholine

6、resynthesizedinto ACh and repackagedinto vesicleACh肌緊張產(chǎn)生的突觸機(jī)制肌緊張產(chǎn)生的突觸機(jī)制 運(yùn)動(dòng)神經(jīng)末梢去極化運(yùn)動(dòng)神經(jīng)末梢去極化 前膜前膜Ca2+通透性通透性 前膜釋放前膜釋放Ach Ach與終板膜受體結(jié)合與終板膜受體結(jié)合 Na+ Ca2+內(nèi)流，內(nèi)流，K+外流外流 EPP AP 興奮收縮耦聯(lián)興奮收縮耦聯(lián)AP (action potential) 膜對(duì)Na+ 、 K+通透性（電導(dǎo)）改變鋒電位鋒電位=Na=Na+ +平衡電位平衡電位AP (action potential)上升支上升支Na+ 內(nèi)流 Na+ 的平衡電位下降支下降支K+ 外流負(fù)后電位K+ 外流暫時(shí)性減弱正后電位Na+