Characterization of the fast sodium current in isolated rat myocardial cells: simulation of the clamped membrane potential.

Abstract
The fast Na inward current of freshly isolated single rat myocardial cells studied by means of the internal perfusion-voltage clamp method. The voltage dependence of this current did not differ from the current-voltage characteristics of the fast Na inward current discribed for other excitable cells and tissues. The time constant of inactivation of the Na+ current of the isolated myocardial cells ranged between 5.2 ms at -58 mV and 0.5 ms at +18 mV. The activation time constant ranged from 0.3 ms at -55 mV to 70 .mu.s at +10 mV. The reactivation time constant of the maximum Na current at a holding potential of -100 mV was found to be 21 .+-. 5 ms. A mathematical model was developed for the stimulation and analysis of the influence of the series and shunt resistances on the time response of the membrane potential. The results of the modeling make it clear that control of the series shunt resistances in any given experiment is a conditio sine qua non for a valid analysis of the kinetic parameters of the Na inward current. Na currents with delayed activation kinetics must be regarded as an indication of insufficient control of the membrane potential.