A Single Channel Description of an Inactivation Deficient Sodium Channel Mutant

Abstract

A characteristic of many voltage-gated ion channels including sodium and potassium channels is that macroscopic currents elicited with a voltage step subsequently decline, or inactivate. Because entry into inactivated states tends to limit the activity of single sodium channels to a small number of openings, identifying the statistical properties of other less stable gating processes can be difficult. Here, we examined the single channel characteristics of a mutant skeletal muscle sodium channel (rat Nav1.4 L435W/L437C/A438W) that exhibits very little macroscopic inactivation (Wang et al., 2003) in response to voltage steps to −60 and −40 mV. Although open dwell time distributions could be more or less described by a single exponential component, both deviations from the single exponential fit and time constants from bi-exponential fits were consistent across patches, suggesting the existence of two open states with time constants of approximately 0.5-1 ms and 2-4 ms. Bursts of openings separated by closures of less than 2 ms were observed frequently, with the number of bursts in a given sweep increasing at more depolarized voltages. The number of opening within each burst was also voltage dependent, increasing from about 3 to 5 openings at −60 and −40 mV, respectively. These data will be presented with a preliminary kinetic description of sodium channel activity in the absence of inactivation. This work was funded by NIH grant GM084140.