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

1. The fast sodium inward current of freshly isolated single rat myocardial cells was studied by means of the internal perfusion-voltage clamp method. 2. The voltage dependence of this current did not differ from the current-voltage characteristics of the fast sodium inward current described for other excitable cells and tissues. 3. The time constant of inactivation of the Na+ current of the isolated myocardial cells ranged between 5.2 msec at -58 mV and 0.5 msec at +18 mV. The activation time constant ranged from 0.3 msec at -55 mV to 70 microseconds at +10 mV. 4. The reactivation time constant of the maximum sodium current at a holding potential of -100 mV was found to be 21 +/- 5 msec. 5. A mathematical model was developed for the simulation and analysis of the influence of the series and shunt resistances on the time response of the membrane potential. The results of the modelling make it clear that control of the series and shunt resistances in any given experiment is a conditio sine qua non for a valid analysis of the kinetic parameters of the sodium inward current. 6. Sodium currents with delayed activation kinetics must be regarded as an indication of insufficient control of the membrane potential.