THEORY OF THE KINETIC-ANALYSIS OF PATCH-CLAMP DATA
THEORY OF THE KINETIC-ANALYSIS OF PATCH-CLAMP DATA
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DOI：
10.1016/s0006-3495(87)83289-7
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发表时间：
1987-12-01
影响因子：
3.4
通讯作者：
KENYON, JL
中科院分区：
文献类型：
--
作者：
BAUER, RJ;BOWMAN, BF;KENYON, JL
本文介绍了膜片钳数据的动力学分析理论。我们假设通道门控是一个马尔可夫过程，它可以用一个由n个动力学状态和每个电压下的n(n-1)个速率常数组成的模型来描述，并且膜片钳数据描述了X个不同电导水平随时间的占据情况。一般而言，一组膜片钳数据中的所有动力学信息可以在描述持续时间的连续驻留时间的观察频率的二维驻留时间直方图中找到(Fredkin，D.R.，M.Montal和J.A.莱斯，1985，The Proceents of the Berkeley Conference in Honor of Jerzy Neyman and Jack Kiefer，Vol.1,269-289)，或者在描述通道在时间t处于给定电导的概率的三点联合概率函数中找到，和时间t+ta1+ta2。对于具有单一打开状态和多个关闭状态的通道的特殊情况，一维分析提供了所有的动力学信息。静态膜片钳数据具有可用于确定H速率常数的信息，其中H=n(n-1)-G，G是电导内速率常数的数目。因此，要计算H速率常数，G速率常数必须是固定的。一般来说，有多组G速率常数可以固定以允许计算H速率常数，尽管不是每组G速率常数都会起作用。任意指定G内导速率常数等于零总是提供解决方案和H速率常数的计算。非静态膜片钳数据具有用于确定参考电压下的H速率常数加上所有测试电压下的n(n-1)速率常数的信息。因此，非平稳数据具有关于速率常数的电压依赖关系的额外信息，这些信息可用于排除不能基于平稳数据取消资格的动力学模型。
This paper describes a theory of the kinetic analysis of patch-clamp data. We assume that channel gating is a Markov process that can be described by a model consisting of n kinetic states and n(n - 1) rate constants at each voltage, and that patch-clamp data describe the occupancy of X different conductance levels over time. In general, all the kinetic information in a set of patch-clamp data is found in either two-dimensional dwell time histograms describing the frequency of observation of sequential dwell times of durations .tau.1 and .tau.2 (Fredkin, D. R., M. Montal, and J. A. Rice, 1985, Proceedings of the Berkeley Conference in Honor of Jerzy Neyman and Jack Kiefer, vol. 1, 269-289) or in three-point joint probability functions describing the probability that a channel is in a given conductance at time t, and at time t + .tau.1, and a time t + .tau.1 + .tau.2. For the special case of channels with a single open state plus multiple closed states, one-dimensional analyses provide all of the kinetic information. Stationary patch-clamp data have information that can be used to determine H rate constants, where H = n(n - 1) - G and G is the number of intraconductance rate constants. Thus, to calculate H rate constants, G rate constants must be fixed. In general there are multiple sets of G rate constants that can be fixed to allow the calculation of H rate constants although not every set of G rate constants will work. Arbitrary assignment of the G intraconductance rate constants equal to zero always provides a solution and the calculation of H rate constants. Nonstationary patch-clamp data have information for the determination of H rate constants at a reference voltage plus n(n - 1) rate constants at all test voltages. Thus, nonstationary data have extra information about the voltage dependencies of rate constants that can be used to rule out kinetic models that cannot be disqualified on the basis of stationary data.