ANALYSIS OF MULTICHANNEL PATCH-CLAMP RECORDINGS BY HIDDEN MARKOV-MODELS

Conventional methods of analysis do not allow the kinetics of patch cl amped ion channels to be completely determined if more than one channe l is present in the patch. This hinders investigations on small ion ch annels as well as on channel cooperativity and the homogeneity of chan nel populations. We present a method to extract the rate constants and current amplitudes for each individual channel from multichannel patc hes by a one-step procedure. For this purpose, the current record is m odeled by the superposed Markov processes of the opening and closing o f each channel that is contaminated by noise (Hidden Markov Model). Ch annel parameters are obtained by maximum likelihood methods. Because t he parameters can be calculated directly from the unfiltered record, t he dwell time and missed event problems are widely diminished. Confide nce bounds for the estimated parameters are given. Statistical tests t o decide whether channels switch identically and/or independently are introduced. The application of the method is demonstrated with simulat ed data.