The sodium currents of nerve under voltage clamp as heterogeneous kinetics. A model that is consistent with possible...

A model is presented which explains in Na+ currents of voltage-clamped nerve as resulting from a heterogeneous initiation of a sequential kinetic process. This is in analogy with the heterogeneity of the kinetics of other dielectric relaxations. The results suggest that: (1) The kinetic processes responsible for the voltage response occur within the membrane rather than at the surface; (2) The heterogeneity is due to simultaneous thermal diffusion and electric field-induced charge migration: (3) The slow turnoff upon prolonged depolarization is a voltage-independent, thermally controlled process; (4) The fast turnoff upon instantaneous repolarization is the reverse of the turning-on process. All the kinetic parameters depend on the transmembrane potential in accord with the possible behavior expected from activated-state theory. The diffusion coefficient of the charged species in the membrane as found from the data agrees with that found by photobleaching experiments on general proteins in membranes. The charge on the molecule responsible for the heterogeneous "gating' can be calculated unambiguously from the data.