ESTIMATING SINGLE-CHANNEL KINETIC-PARAMETERS FROM IDEALIZED PATCH-CLAMP DATA CONTAINING MISSED EVENTS

We present here a maximal likelihood algorithm for estimating single-c hannel kinetic parameters from idealized patch-clamp data. The algorit hm takes into account missed events caused by limited time resolution of the recording system. Assuming a fixed dead time, we derive an expl icit expression for the corrected transition rate matrix by generalizi ng the theory of Roux and Sauve (1985, Biophys. J, 48:149-158) to the case of multiple conductance levels. We use a variable metric optimize r with analytical derivatives for rapidly maximizing the likelihood. T he algorithm is applicable to data containing substates and multiple i dentical or nonidentical channels. It allows multiple data sets obtain ed under different experimental conditions, e,g,, concentration, volta ge, and force, to be fit simultaneously. It also permits a variety of constraints on rate constants and provides standard errors for all est imates of model parameters, The algorithm has been tested extensively on a variety of kinetic models with both simulated and experimental da ta, II is very efficient and robust; rate constants for a multistate m odel can often be extracted in a processing time of approximately 1 mi n, largely independent of the starting values.