Characterization of the sodium currents in isolated human cardiocytes

Abstract

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 MΩ). 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 −72.2±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±2.9ms 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 μM. It is concluded that the properties of human cardiac Na⁺ channels are similar to those of the juvenile Na⁺ channels of human skeletal muscle.