Sodium current in isolated human ventricular myocytes

Although fast sodium current (I(Na)) plays a major role in the generation and conduction of the cardiac impulse, the electrophysiological characteristics of I(Na) in isolated human ventricular myocytes have not yet been fully described. We characterized the human ventricular I(Na) of enzymatically isolated myocytes using whole cell voltage-clamp techniques. Sixty myocytes were isolated from ventricular specimens obtained from 22 patients undergoing open-heart surgery. A low temperature (17°C) and Na⁺ concentration in the external solution (5 or 10 mM) allowed good voltage control and facilitated the measurement of I(Na). Cs⁺ was substituted for K⁺ in both internal and external solutions to block K⁺ currents, and F^- was added to the internal solution to block Ca²⁺ current. I(Na) was activated at a voltage threshold of approximately -70 mV, and maximal inward current was obtained at approximately -30 mV (holding potential = -140 mV). The voltage dependence of steady-state I(Na) availability (h(α)) was sigmoidal with half inactivation occurring at -97.3 ± 1.1 mV and a slope factor of 5.77 ± 0.10 mV (n = 60). We did not detect any significant differences in these parameters in cells from patients with a variety of disease states, with or without congestive heart failure. The overlap in voltage dependence of h(α) and Na⁺ conductance suggested the presence of a Na⁺ 'window' current. An inactivation time course was voltage dependent and was fitted best by the sum of two exponentials. The rate of recovery from inactivation also was voltage dependent and fitted by the sum of two exponentials. The kinetics of inactivation did not vary with disease state. Sensitivity to tetrodotoxin was similar to that of other mammalian cardiac cells, with a resting state apparent dissociation constant of 1.7 μM (n = 6). In summary, our results demonstrate that the I(Na) of normal-appearing, Ca²⁺-tolerant human ventricular myocytes is very similar to that in human atrial myocytes that we reported previously as well as to that of both atrial and ventricular cells from other mammalian species.