Hawkes A G, Jalali A, Colquhoun D
Statistics and Operational Research Group, European Business Management School, University of Wales, Swansea, U.K.
Philos Trans R Soc Lond B Biol Sci. 1992 Sep 29;337(1282):383-404. doi: 10.1098/rstb.1992.0116.
The openings and shuttings of individual ion channel molecules can be described by a Markov process with discrete states in continuous time. The predicted distributions of the durations of open times, shut times, bursts of openings, etc. are all described, in principle, by mixtures of exponential densities. In practice it is usually found that some of the open times, and the shut times, are too short to be detected reliably. If a fixed dead-time tau is assumed then it is possible to define, as an approximation to what is actually observed, an 'extended opening' or e-opening which starts with an opening of duration at least tau followed by any number of openings and shuttings, all the shut times being shorter than tau; the e-opening ends when a shut time longer than tau occurs. A similar definition is used for e-shut times. The probability densities, f(t), of these extended times have previously been obtained as expressions which become progressively more complicated, and numerically unstable to compute, as t-->infinity. In this paper we present, for the two-state model, an alternative representation as an infinite series of which a small number of terms gives a very accurate approximation of f (t) for large t. For the general model we present an asymptotic representation as a mixture of exponentials which is accurate for all except quite small values of t. Some simple model-independent corrections for missed events are discussed in relationship to the exact solutions.
单个离子通道分子的开放和关闭可以用一个连续时间内具有离散状态的马尔可夫过程来描述。开放时间、关闭时间、开放爆发等持续时间的预测分布原则上都由指数密度的混合来描述。实际上,通常会发现一些开放时间和关闭时间太短,无法可靠检测。如果假设一个固定的死时间τ,那么就有可能定义一个“扩展开放”或e-开放,作为实际观测值的近似值,它从持续时间至少为τ的一次开放开始,接着是任意数量的开放和关闭,所有关闭时间都短于τ;当出现长于τ的关闭时间时,e-开放结束。对e-关闭时间也采用类似的定义。这些扩展时间的概率密度f(t)以前是以表达式的形式得到的,随着t趋于无穷大,这些表达式会变得越来越复杂,计算起来在数值上也不稳定。在本文中,对于两态模型,我们给出了一种替代表示,即一个无穷级数,对于大t,其中少数几项就能给出f(t)的非常精确的近似值。对于一般模型,我们给出了一种渐近表示,即作为指数的混合,除了t非常小的值外,对于所有t都很精确。还结合精确解讨论了一些与漏检事件无关的简单模型修正。