Ball F G, Chen A, Sansom M S
Department of Mathematics, University of Nottingham, University Park, U.K.
Proc Biol Sci. 1992 Dec 22;250(1329):263-9. doi: 10.1098/rspb.1992.0158.
Patch-clamp recording allows investigations of the gating kinetics of single ion channels. Statistical analysis of kinetic data can enhance our understanding of channel gating at a molecular level. Experimental channel records suffer from time interval omission, i.e. failure to detect brief channel openings and closings. It is important to incorporate this phenomenon into statistical analyses of ion channel data. When time interval omission is ignored, the method of maximum likelihood can usually be used to estimate gating parameters from a single channel record. However, it is far more difficult to apply this method when time interval omission is incorporated. We present an alternative approach to parameter estimation based on Poisson sampling. A simulated homogeneous Poisson process is superimposed onto the channel record and inference is based on the numbers of points in successive open and closed sojourns, rather than on the sojourn times themselves. We describe the method for the two-state Markov model C<-->O, although it is applicable to more general models. Computer-simulated data are used to demonstrate the efficacy of the method. Modifications of the method are discussed briefly.
膜片钳记录可用于研究单个离子通道的门控动力学。对动力学数据进行统计分析能够增强我们在分子水平上对通道门控的理解。实验性通道记录存在时间间隔遗漏的问题,即未能检测到短暂的通道开放和关闭。将这种现象纳入离子通道数据的统计分析中很重要。当忽略时间间隔遗漏时,通常可以使用最大似然法从单个通道记录中估计门控参数。然而,当纳入时间间隔遗漏时,应用此方法要困难得多。我们提出了一种基于泊松抽样的参数估计替代方法。将一个模拟的齐次泊松过程叠加到通道记录上,并且推断是基于连续开放和关闭逗留期内的点数,而不是基于逗留期本身。我们描述了适用于两态马尔可夫模型C<-->O的方法,尽管它适用于更一般的模型。使用计算机模拟数据来证明该方法的有效性。简要讨论了该方法的改进。