Estimation of fractional changes in peak gNa, -gNa, ENa, and h infinity (V) of cardiac cells from Vmax of the propagating action potential.

Fractional changes in the peak sodium conductances of the cardiac cell membrane during the action potential are often estimated from fractional changes in Vmax. The present model study shows, in reasonable accord with experimental evidence, that this approach is valid for propagating action potentials provided that the membrane capacitance does not change and that the nonsodium current is small at the time of Vmax. When the maximum conductance of the sodium channel (gNa) and the sodium equilibrium potential (ENa) are varied independently of one another, fractional changes in either of them can be predicted from fractional changes in Vmax if a reasonable estimate of the initial value of ENa is available. Manipulations which modify the resting membrane potential without changing gNa allow to calculate fractional changes in the steady-state Na+ inactivation [h infinity (V)] when ENa is known. Simulation runs were carried out for a continuous cable and a discontinuous cable with either a low (1 omega.cm2) or a high (10 omega.cm2) junctional resistance. The predictions of the model are valid in the discontinuous cable provided that the recording point remains strictly the same throughout the series of measurements. Because the high-resistance discontinuous cable provides conditions which reduce further the nonsodium current at the time of Vmax, the accuracy of the predictions are better in this case. It is concluded that properly designed experimental approaches based on Vmax measurements can yield important information on manipulations affecting gNa, ENa, and h infinity (V) during propagation, and that a better accuracy is possible in cardiac muscle when measurements are made during transverse propagation.