Using Vmax to estimate changes in the sodium membrane conductance in cardiac cells

Relative changes in the sodium conductance of the resting cardiac cell membrane are often estimated from relative changes in the maximum rate of rise of the action potential (Vmax). This approach has given rise to some controversy and it has not been possible so far to test it directly on an experimental basis. We have examined here the validity of this estimation using three different Hodgkin-Huxley representations of the cardiac membrane sodium current. The two basic requirements are a constant membrane capacitance and a negligible relative value of the nonsodium membrane currents at the time of Vmax. It is shown further that the approach leads to a satisfactory estimation only when the latency of Vmax is kept constant and a correction factor for the sodium driving force is applied to Vmax measurements. This conclusion applies either to a nonpropagated action or to an action potential propagated at constant velocity, provided that the membrane is not too strongly depolarized. It is valid for a wide range of sodium equilibrium potentials and a range of maximum sodium conductances limited to about 50% of the nominal value.