Statistical properties of single sodium channels.

Abstract

Single channel currents were obtained from voltage-activated Na channels in outside-out patches of tissue-cultured GH3 cells, a clonal line from rat pituitary gland. In membrane patches where the probability of overlapping openings was low, the open time histograms were well fit by a single exponential. Most analysis was done on a patch with exactly one channel. No evidence was found for multiple open states at -25 and -40 mV, since open times, burst durations and autocorrelation functions were time independent. Amplitude histograms showed no evidence of multiple conductance levels. The gating was fit with 25 different time-homogeneous Markov chain models having up to 5 states, using a maximum likelihood procedure to estimate the rate constants. For selected models, this procedure yielded excellent predictions for open time, close time, and 1st latency density functions, as well as the probability of the channel being open after a step depolarization, the burst duration distribution, autocorrelation, and the distribution of number of openings/record. The models were compared statistically using likelihood ratio tests and Akaike''s information criterion. Acceptable models allowed inactivation from closed states, as well as from the open state. Among the models eliminated as unacceptable by this survey were the Hodgkin-Huxley model and any model requiring a channel to open before inactivating.