Kinetic models suggest bimolecular reaction steps in axonal Na+-channel gating

Abstract kinetic models that can successfully simulate the ion-permeability features of axonal Na+ channels suggest the presence of bimolecular reaction steps in the activation of the channels. A chemically plausible interpretation of minimum complexity is described. The implied chemical formalism is highly suggestive of an activator-controlled gating system with strong similarities to the acetylcholine-regulated system. Conformational changes that underlie the ion-conductance changes are suggested to possess a greater sensitivity to the membrane field in axonal parts of excitable membranes than at synaptic parts. This would allow axonal permeability changes to be energetically regulated more conservatively than is observed for synaptic ion channels. Axonal K+ channels with delayed activation kinetics would serve to reverse the increase in membrane permeability to Na+ with a minimum of chemical dissipation.