Wathey J C, Nass M M, Lester H A
Biophys J. 1979 Jul;27(1):145-64. doi: 10.1016/S0006-3495(79)85208-X.
To test our present quantitative knowledge of nicotinic transmission, we reconstruct the postsynaptic conductance change that results after a presynaptic nerve terminal liberates a quantum of acetylcholine (ACh) into the synaptic cleft. The theory assumes that ACh appears suddenly in the cleft and that is subsequent fate is determined by radial diffusion, by enzymatic hydrolysis, and by binding to receptors. Each receptor has one channel and two ACh binding sites; the channel opens when both sites are occupied and the rate-limiting step id the binding and dissociation of the second ACh molecule. The calculations reproduce the experimentally measured growth phase (200 microseconds), peak number of open channels (2,000), and exponential decay phase. The time constant of the decay phase exceeds the channel duration by approximately equal to 20%. The normal event is highly localized: at the peak, two-thirds of the open channels are within an area of 0.15 micrometer 2. This represents 75% of the available channels within this area. The model also simulates voltage and temperature dependence and effects of inactivating esterase and receptors. The calculations show that in the absence of esterase, transmitter is buffered by binding to receptors and the postsynaptic response can be potentiated.
为了检验我们目前关于烟碱样传递的定量知识,我们重构了突触后电导变化,该变化是在突触前神经末梢向突触间隙释放一个乙酰胆碱(ACh)量子后产生的。该理论假设ACh突然出现在突触间隙中,其随后的命运由径向扩散、酶促水解以及与受体结合决定。每个受体有一个通道和两个ACh结合位点;当两个位点都被占据时通道打开,限速步骤是第二个ACh分子的结合和解离。这些计算重现了实验测量的生长阶段(200微秒)、开放通道的峰值数量(2000个)以及指数衰减阶段。衰减阶段的时间常数比通道持续时间长约20%。正常事件高度局限:在峰值时,三分之二的开放通道位于0.15平方微米的区域内。这占该区域内可用通道的75%。该模型还模拟了电压和温度依赖性以及失活酯酶和受体的影响。计算表明,在没有酯酶的情况下,递质通过与受体结合而被缓冲,并且突触后反应可以增强。