Inactivation viewed through single sodium channels.
Inactivation viewed through single sodium channels.
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通过单钠通道观察失活。
DOI：
10.1085/jgp.84.4.535
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Horn,R
中科院分区：
文献类型：
--
作者：
Vandenberg,CA;Horn,R
对组织培养的GH3细胞钠电流的记录表明，整个细胞和平均单通道记录的失活率与电压有关：tau h变化e倍/约26 mV。在一个五态动力学模型中，通过检查通过单通道记录的最大似然分析估计的各个速率常数的电压相关性，研究了这种电压依赖性的来源。从开放状态失活的速率常数，而不是闭合，随着去极化而增加，开放通道失活的概率也是如此。从打开状态关闭的速率常数具有相反的电压依赖关系。这两个速率常数都对平均打开时间有贡献，而平均打开时间与电压的关系不大。当电压达到-20 mV时，开启时间和猝发持续时间都小于tau h。最慢的激活时间常数tau m是从整个细胞记录中测量的，通过将单个指数与尾部电流或胰酶处理的细胞中的激活电流进行拟合，在这种情况下，失活被取消。当电压大于-35 mV，但小于tau h时，与tau h有相似的电压依赖关系。当电压大于-10 mV时，单个通道在失活前可多次开启和关闭。因此，与去极化引起的宏观电流相对应的平均单通道记录最好通过第一潜伏期密度与自相关函数的卷积而不是与1(通道开放时间分布)的卷积来描述。除激活过程外，从开态失活的电压依赖性也是决定宏观失活的电压依赖性的重要因素。虽然激活和失活的速度有很大的重叠，但在所考察的两个模型中，独立失活和耦合失活不能在统计上区分。尽管激活速率影响在中等电压下观察到的失活速率，但对速率常数的估计外推表明，在非常去极化的电压下，激活过程如此之快，以至于在失活时间过程中它是一个微不足道的因素。门控电流的预测表明，固有的电压相关的钝化过程不需要在门控电流中产生明显的分量。
Recordings of the sodium current in tissue-cultured GH3 cells show that the rate of inactivation in whole cell and averaged single channel records is voltage dependent: tau h varied e-fold/approximately 26 mV. The source of this voltage dependence was investigated by examining the voltage dependence of individual rate constants, estimated by maximum likelihood analysis of single channel records, in a five-state kinetic model. The rate constant for inactivating from the open state, rather than closing, increased with depolarization, as did the probability that an open channel inactivates. The rate constant for closing from the open state had the opposite voltage dependence. Both rate constants contributed to the mean open time, which was not very voltage dependent. Both open time and burst duration were less than tau h for voltages up to -20 mV. The slowest time constant of activation, tau m, was measured from whole cell records, by fitting a single exponential either to tail currents or to activating currents in trypsin-treated cells, in which the inactivation was abolished. tau m was a bell-shaped function of voltage and had a voltage dependence similar to tau h at voltages more positive than -35 mV, but was smaller than tau h. At potentials more negative than about -10 mV, individual channels may open and close several times before inactivating. Therefore, averaged single channel records, which correspond with macroscopic current elicited by a depolarization, are best described by a convolution of the first latency density with the autocorrelation function rather than with 1 - (channel open time distribution). The voltage dependence of inactivation from the open state, in addition to that of the activation process, is a significant factor in determining the voltage dependence of macroscopic inactivation. Although the rates of activation and inactivation overlapped greatly, independent and coupled inactivation could not be statistically distinguished for two models examined. Although rates of activation affect the observed rate of inactivation at intermediate voltages, extrapolation of our estimates of rate constants suggests that at very depolarized voltages the activation process is so fast that it is an insignificant factor in the time course of inactivation. Prediction of gating currents shows that an inherently voltage-dependent inactivation process need not produce a conspicuous component in the gating current.