Voltage-dependent gating of single sodium channels from mammalian neuroblastoma cells

Single sodium channel currents have been studied in cell-attached patches from the mouse neuroblastoma cell line N1E115. Distributions of open duration, latency until first opening, and the average probability of a channel being open after a voltage step, p(t), were analyzed and compared to predicted distributions from various kinetic models for voltage-dependent gating. It was found that, over most of the voltage range under which channel gating occurs, the slow steps in gating are opening transitions and that inactivation of open channels is significantly faster than the decline in p(t) (tau h). This view of gating is confirmed by comparison of the kinetics of ensemble averages of single-channel currents obtained from step- and tail-current records at the same voltage. The probability of a channel reopening after having closed was calculated by comparing p(t) with the convolution of the first-latency probability density and the conditional probability of remaining open t milliseconds after opening. This reopening probability is small but slightly voltage dependent over the voltage range where the mean open duration remains constant and tau h changes considerably. The voltage dependence of open channel inactivation and deactivation were calculated from the probability of reopening and the mean open duration. The equivalent gating charge for the inactivation rate is a few tenths of an electronic charge, whereas the equivalent charge for the closing rate is 2.5-3.5 electronic charges.