Ionic dependence of sodium currents in squid axons analyzed in terms of specific ion "channel" interactions

Inward sodium currents were measured from voltage-clamped giant axons externally perfused with artificial seawater (ASW) solutions containing various concentrations of sodium and potassium ions. The data was analyzed under the assumption that under a constant membrane potential sodium conductance is determined by a specific ion-channel site (SIS) reaction. The sodium current density values were expressed in terms of SIS-reaction rates which were compared, by means of minimization techniques, with those computed for various saturation reaction mechanisms. The following conclusions were drawn: 1) The dependence of peak inward sodium current on external sodium and potassium concentrations can be described in terms of saturation reactions. 2) The experimental data fit well the kinetics of a positive cooperative homotropic reaction, involving at least two allosteric active sites. One of these sites may be catalytic while the other, either catalytic or regulatory. 3) The inhibitory effect of external potassium on inward sodium current, can be described by a reversible competitive or noncompetitive inhibition mechanism. The values of the dissociation constant of the inhibitor-site "complex" (Ki) were found to be close to the external potassium concentration under physiological conditions.