Gating charge immobilization and sodium current inactivation in internally perfused crayfish axons

Abstract

The sodium permeability in nerve is regulated by two gating processes, activation and inactivation¹. Their relationship to one another has been described as ‘independent’¹ or ‘coupled’^2,3. An independent model, the Hodgkin and Huxley formulation, makes two testable predictions regarding gating current. First, as inactivation is voltage sensitive, it requires its own voltage sensor and might be expected to generate its own gating current. Second, gating current associated with activation should be unaffected by inactivation. Although charge movement associated with sodium activation is well characterized⁴, no inactivation charge movement has been described. Instead, depolarizations long enough to produce sodium current inactivation were found to diminish the charge movement associated with channel closing⁵. Inactivation temporarily immobilized a substantial fraction of the gating charge. These observations suit a coupled model in which inactivation gains its voltage dependence by coupling to activation³, and inactivation may in turn influence activation. However, the relative time course of the development immobilization (τ_immob) was found to be the same³, the same in some voltage ranges⁶ and slower than that for inactivation (τ_inact). In crayfish axons inactivation is roughly five times faster than in squid, providing an interesting opportunity to compare inactivation and immobilization. Further, inactivation is so rapid that inactivation gating current should be easily visible. No inactivation charge movement was found and τ_immob equals τ_inact.