Rapid kinetic analysis of multichannel records by a simultaneous fit to all dwell-time histograms

Abstract

A method is presented for rapidly extracting single-channel transition rate constants from patch-clamp recordings containing signals from several channels. The procedure is based on a simultaneous fit of the observed dwell- time distributions for all conductance levels, using a maximum likelihood approach. This algorithm allows estimation of single-channel rate constants in cases where more advanced methods may be impractical because of their extremely long computational time. A correction is included for the limited time resolution of the recording system, according to theory developed by Roux and Sauve (Biophys. J. 48:149-158, 1985), by accounting for the impact of undetected transitions on the dwell-time distributions, and by introducing an improved practical implementation of a fixed dead time for the case of more than one channel. This feature allows application of the method to noisy data, after filtering. A computer program implementing the method is tested successfully on a variety of simulated multichannel current traces.