ESTIMATING KINETIC-PARAMETERS FOR SINGLE CHANNELS WITH SIMULATION - A GENERAL-METHOD THAT RESOLVES THE MISSED EVENT PROBLEM AND ACCOUNTS FOR NOISE
ESTIMATING KINETIC-PARAMETERS FOR SINGLE CHANNELS WITH SIMULATION - A GENERAL-METHOD THAT RESOLVES THE MISSED EVENT PROBLEM AND ACCOUNTS FOR NOISE
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DOI：
10.1016/s0006-3495(90)82487-5
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发表时间：
1990-12-01
影响因子：
3.4
通讯作者：
WEISS, DS
中科院分区：
文献类型：
--
作者：
MAGLEBY, KL;WEISS, DS
从单个通道记录的电流分析由于数据的时间分辨率有限（滤波）而变得复杂，这可能会阻止短间隔的检测。虽然在识别动力学模型和估计参数时，已经使用了许多方法来纠正未检测到的间隔（错过的事件），但它们都没有提供一个考虑到噪声和有限时间分辨率的真实影响的通用方法。本文提出了这样一种方法。该方法是使用模拟的单通道电流来合并滤波和噪声对错过事件和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分析模拟电流。利用从模拟和实验单通道电流中获得的二维停留时间分布的似然比较的迭代搜索过程，然后允许确定最可能的速率常数。迭代模拟方法排除了由更典型的无噪声和绝对死区时间（理想滤波）假设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该增加区分不同门控机制的能力。迭代模拟方法一般适用于通常打开到单个电导电平的通道。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。
Analysis of currents recorded from single 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 mechanisms or the form of the predicted dwell-time distributions.