Analyzing stochastic events in multi-channel patch clamp data

Abstract

In an effort to understand the gating properties of ionic channels in biological membranes, an efficient method was developed to estimate the kinetic constants from opening-closing events of the channels. Our method is suitable to single channel patch-clamp recordings that contain several ionic channels functioning simultaneously. It is different from the maximum likelihood method previous developed by Horn and Lange, in that our method is a continuum approach and makes uses of analytic expressions of the probability density functions of the event times. Combinatorial analysis was necessary to correctly include more typical multi-channel recordings. This yields computationally quicker results than the method of Horn and Lange, which uses a discretized time series. Model-dependent portions of the code are minimal and easily modified. To illustrate the goodness of our method, we have generated the open-close processes of the patch-clamp records on a digital computer using the exponential random number generators. For multi-channel patches, we have introduced a few plausible approximations to make our algorithm more efficient. The soundness of the our approximations were tested with such measures as the fraction of the open state at time t, p _open(t), and frequencies of the number of openings per run. A copy of the computer code implementing this algorithm can be obtained from the authors.