Asymmetric displacement currents in giant axons and macromolecular gating processes.

An electrical-chemical gating model is proposed that describes basic observations on asymmetric displacement currents and transient Na+ conductivity changes in squid giant axons. A previously developed single-parameter analysis of primary voltage clamp data yields normal mode relaxation times that agree well with the time constants of asymmetric capacitative currents, suggesting these currents as gating currents associated with charge displacement in a subunit of a complex gating system. The physical-chemical approach correlates the opening of Na+ channels with charge-charge interactions amongst displaceable membrane charges or dipoles and conformational changes in gating macromolecules. The model covers the close correspondence between the voltage dependence of the peak value of the Na+ conductance change and that of the square of the total displaced charge for small depolarizing voltage steps. The quadratic charge relationship also describes the two-mode relaxation of asymmetric displacement currents; the transiently inhibited return transition of two-thirds of the displaced charge after a prolonged depolarization is interpreted to reflect a dissipative chemical gating process.