神经肌肉传导电生理.ppt

神经肌肉传导电生理 Acetylcholine curare是一种取自热带植物的剧毒药物，被南美的土著猎人用作制作毒箭的材料 Acetylcholine Bernard 认为 Curare 的作用位点是神经与肌肉相接触的区域（ＮＭＪ） John Langley 发现Nicotine 能刺激蛙的离体骨骼肌的收缩，但Curare 会使Nicotine 失效 1906 John Langley 提出化学递质假说 1921 Loewi 发现化学递质－Ach Acetylcholine 神经-肌接头NMJ (neuromuscular junction) 运动区皮质 皮质脊髓纤维 皮质脊髓束 脊髓前角运动神经元 突触连接 NMJ 骨骼肌 nAchR Arthur Karlin nAchR是一个五聚体 α亚基 2个 β、 δ亚基各一个 ε或γ亚基 nAchR nAchR  nAchR Immature Spread Unstable ? life 24 hrs Longer burst duration Smaller conductance 2-10 times longer channel opening (slow closing) Mature Localized Stable ? life 2 weeks Burst activity Normal conductance Channel opens for 0.5 millisecond nAchR 10 % receptors must be open for muscle action potential generation 70 % receptors can be occupied before fade is observed 95 % receptor occupancy required for complete twitch suppression NMJ突触机制 肌紧张产生的突触机制 运动神经末梢去极化 ? 前膜Ca2+通透性? ? 前膜释放Ach ? Ach与终板膜受体结合 ? Na+ Ca2+内流，K+外流 ? EPP ? AP ?兴奋收缩耦联 AP (action potential) 膜对Na+ 、 K+通透性（电导）改变 锋电位=Na+平衡电位 AP (action potential) 上升支 Na+ 内流 Na+ 的平衡电位 下降支 K+ 外流 负后电位 K+ 外流暂时性减弱 正后电位 Na+-K+泵的活动 总 结 Ach nAchR NMJ AP * Presynaptic Ach receptors similar to postsynaptic except there is Alpha-3 than Alpha-1 Burst in Ach receptors is about 5 in mature and 3-6 times more in immature. Single channel conductance is 60% of normal in immature curare ACh Alpha Alpha Epsilon / Gamma Delta Beta Ion Channel ACh In fetal denervated receptors: Gamma replaces Epsilon NMJ突触机制 K+ Na+ Ca2+ NMJ突触机制 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+ ACh ACh ACh ACh Na+ Na+ K+ Muscle membrane Nerve terminal Ca2+ Ca2+ EPP AP Muscle membrane Presynaptic terminal Muscle Membrane Voltage (mV) Time (msec) -90 mV VK VNa 0 Threshold Presynaptic AP EPP ACh Receptor Channels Voltage-gated Na Channels Inward Rectifier K Channels Meanwhile ... ACh ACh unbinds from its receptor Muscle membrane ACh so the channel closes ACh ACh Nerve terminal ACh is hydroly