Voltage dependence of rate functions for Na+ channel inactivation within a membrane

TL;DR

This paper investigates how voltage influences the rate functions of Na+ channel inactivation, linking molecular mechanisms to Hodgkin-Huxley models, and derives voltage-dependent rate functions from a master equation approach.

Contribution

It introduces a model connecting voltage sensor activation to a two-stage inactivation process, deriving rate functions consistent with empirical Hodgkin-Huxley data.

Findings

Rate functions depend on voltage and saturate at extreme potentials.

Derived rate functions align with Hodgkin-Huxley empirical expressions.

Model links molecular activation to macroscopic current behavior.

Abstract

The inactivation of a Na+ channel occurs when the activation of the charged S4 segment of domain DIV is followed by the binding of an intracellular hydrophobic motif which blocks conduction through the ion pore. The voltage dependence of Na+ channel inactivation is, in general, dependent on the rate functions of the S4 sensors of each of the domains DI to DIV. If the activation of a single voltage sensor that regulates the Na+ channel conductance is coupled to a two-stage inactivation process, the rate functions for inactivation and recovery from inactivation, as well as the time dependence of the Na+ current in terms of the variables m(t) and h(t), may be derived from a solution to the master equation for interdependent activation and inactivation. The rate functions have a voltage dependence that is consistent with the Hodgkin-Huxley empirically determined expressions, and exhibit saturation for both depolarized and hyperpolarized clamp potentials.