CHARACTERIZATION OF THE SODIUM CURRENTS IN ISOLATED HUMAN CARDIOCYTES

The whole-cell recording technique was used to register Na+ currents from 403 atrial cardiocytes isolated from 80 human biopsies. With intracellular [Na+] ([Na+](i)) raised to 70 mM, and at physiological extracellular [Na+] ([Na+](e), 145 mM) and room temperature, the Na+ currents were small enough for the error of the voltage clamp not to exceed 2 mV (series resistances 0.4-2 M Ohm). The threshold potential of the Na+ current was -64.0+/-7.7 mV. The peak amplitude was at -30.0+/-6.2 mV. The time course of fast inactivation was satisfactorily described with a single exponential. The time constant of inactivation was 2.0 ms at -55 mV and asymptotically approached 0.2 ms at positive membrane potentials. The steady-state inactivation curve was well fitted by a single Boltzmann distribution. Increasing the prepulse duration from 32 to 512 ms shifted the inflexion point of the curve from -61.7+/-6.4 to +2.6 mV. The time course of slow inactivation was also well described by a single exponential, the time constant ranging from 76.1+/-29.3 ms at -115 mV to 18.6+/-7.8 ms at -55 mV. Fitting the time course of recovery from inactivation required two time constants. At a recovery potential of -135 mV these were 1.6+/-0.2 and 8.6+/-2.9 ms and 15.9+/-9.4 and 53.2+/-33.3 ms at -95 mV. A 50% block of the Na+ currents was achieved by tetrodotoxin at 10 mu M. It is concluded that the properties of human cardiac Na+ channels are similar to those of the juvenile Na+ channels of human skeletal muscle.