Does the maximum upstroke velocity of the action potential (Vmax) represent available sodium conductance in frog...

In examining the relation between the maximum upstroke velocity of the action potential (Vmax) and available Na conductance (agNa), the dose-response curve for tetrodotoxin (TTX) and the steady-state inactivation (h infinity)-membrane potential curve were obtained by measuring Na current (INa) as well as Vmax in single isolated frog ventricular cells. The present experiment demonstrated that the relation between Vmax and agNa is linear. On the other hand, simulation analysis of this relation in the absence of leakage current (IL), in which the necessary parameters for INa had been determined by the voltage clamp experiment, showed non-linear properties. The non-linear relation originates from the fact that kinetic variable, m, and driving force for INa at the time of Vmax is not constant with respect to the change in either hO or gNa. A reasonable explanation for this discrepancy is that the presence of IL suppresses the total ionic current at the time of Vmax and hence the change in INa does not straightforwardly reflect that in Vmax.