A proposed physical explanation of the activation of sodium channels

A physical mechanism for activation of excitable Na channels is proposed, based on an electrodiffusion model with the assumption of constant dielectric permittivity replaced with a dielectric equation of state descriptive of ferroelectric behavior. The model postulates a ferroelectric channel unit within the glycoprotein Na channel to be in a ferroelectric state in a membrane at resting potential as a result of field-induced elevation of the transition temperature. A threshold depolarization initiates a first-order transition to a paraelectric state. A screening layer of permeant cations is drawn across the membrane by the negative bound charge at the phase boundary. This hypothesis is consistent with experimental observations of current-voltage hysteresis, voltage-dependent birefringence, single-channel currents, “gating” currents, heat and cold block of excitability, electromechanical and thermoelectric responses, and nonlinear ion conduction, and in quantitative agreement with the estimated magnitude of the surface charge of the channel.