Does the Maximum Upstroke Velocity of the Action Potential (V_max) Represent Available Sodium Conductance in Frog Ventricular Cells?

Abstract

In examining the relation between the maximum upstroke velocity of the action potential (V_max) and available Na conductance (ag_Na), the dose-response curve for tetrodotoxin (TTX) and the steady-state inactivation (h_∞)-membrane potential curve were obtained by measuring Na current (I_Na) as well as V_max in single isolated frog ventricular cells. The present experiment demonstrated that the relation between V_max and ag_Na is linear. On the other hand, simulation analysis of this relation in the absence of leakage current (I_L), in which the necessary parameters for I_Na 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 I_Na at the time of V_max is not constant with respect to the change in either h₀ or g_Na. A reasonable explanation for this discrepancy is that the presence of I_L suppresses the total ionic current at the time of V_max and hence the change in I_Na does not straightforwardly reflect that in V_max.