An ion-site interaction model for sodium currents in the giant axon.

The time and voltage dependence of sodium currents in the Myxicola giant axon were examined as functions of the external sodium concentration. The results were incompatible with a model of free diffusion through a gated channel, but lent themselves to analysis in terms of a model involving a positive cooperative homotropic reaction in which Na+ interacts with two allosteric sites - a regulatory site and a transfer site - at the 'sodium channel'. The time-dependent solution of the rate equations describing the kinetics of the transfer reaction was derived as an expression describing the sodium current as a function of time, membrane potential and external sodium concentration. This function was used to test the validity of the model by its ability to predict the nerve excitability properties. The predicted i-v and i-t curves fitted the experimental results (p less than 0.005 and p less than 0.05, respectively). The computed parameters of these functions are consistent with other experimental results. The possibility of a noncooperative reaction was rejected.