Magleby K L, Weiss D S
Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101.
Biophys J. 1990 Dec;58(6):1411-26. doi: 10.1016/S0006-3495(90)82487-5.
Analysis of currents recorded from single channels is complicated by the limited time resolution (filtering) of the data which can prevent the detection of brief intervals. Although a number of approaches have been used to correct for the undetected intervals (missed events) when identifying kinetic models and estimating parameters, none of them provide a general method which takes into account the true effects of noise and limited time resolution. This paper presents such a method. The approach is to use simulated single-channel currents to incorporate the true effects of filtering and noise on missed events and interval durations. The simulated currents are then analyzed in a manner identical to that used to analyze the experimental currents. An iterative search process using likelihood comparison of two-dimensional dwell-time distributions obtained from the simulated and experimental single-channel currents then allows the most likely rate constants to be determined. The large errors and false solutions that can result from the more typically applied assumptions of no noise and an absolute dead time (idealized filtering) are excluded by the iterative simulation method, and the correlation information contained in the two-dimensional distributions should increase the ability to distinguish among different gating mechanisms. The iterative simulation method is generally applicable to channels which typically open to a single conductance level. For these channels the method places no restrictions on the proposed gating mechanism or the form of the predicted dwell-time distributions.
单通道记录电流的分析因数据有限的时间分辨率（滤波）而变得复杂，这可能会妨碍对短暂间隔的检测。尽管在识别动力学模型和估计参数时，已采用多种方法来校正未检测到的间隔（漏检事件），但这些方法均未提供一种能考虑噪声和有限时间分辨率真实影响的通用方法。本文提出了这样一种方法。该方法是利用模拟单通道电流来纳入滤波和噪声对漏检事件及间隔持续时间的真实影响。然后，以与分析实验电流相同的方式对模拟电流进行分析。通过对从模拟和实验单通道电流获得的二维驻留时间分布进行似然比较的迭代搜索过程，进而确定最可能的速率常数。迭代模拟方法排除了因更典型的无噪声和绝对死时间（理想化滤波）假设可能导致的大误差和错误解，并且二维分布中包含的相关信息应能增强区分不同门控机制的能力。迭代模拟方法通常适用于通常开放至单一电导水平的通道。对于这些通道，该方法对所提出的门控机制或预测驻留时间分布的形式没有限制。
