SODIUM CURRENT IN ISOLATED HUMAN VENTRICULAR MYOCYTES

Although fast sodium current (I(Na)) plays a major role in the generat ion and conduction of the cardiac impulse, the electrophysiological ch aracteristics 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 te chniques. Sixty myocytes were isolated from ventricular specimens obta ined from 22 patients undergoing open-heart surgery. A low temperature (17-degrees-C) and Na+ concentration in the external solution (5 or 1 0 mM) allowed good voltage control and facilitated the measurement of I(Na). Cs+ was substituted for K+ in both internal and external soluti ons 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 app roximately -70 mV, and maximal inward current was obtained at approxim ately -30 mV (holding potential = -140 mV). The voltage dependence of steady-state I(Na) availability (h(infinity)) 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 sta tes, with or without congestive heart failure. The overlap in voltage dependence of h(infinity) and Na+ conductance suggested the presence o f a Na+ ''window'' current. An inactivation time course was voltage de pendent and was fitted best by the sum of two exponentials. The rate o f 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 o f other mammalian cardiac cells, with a resting state apparent dissoci ation constant of 1.7 muM (n = 6). In summary, our results demonstrate that the I(Na) of normal-appearing, Ca2+-tolerant human ventricular m yocytes is very similar to that in human atrial myocytes that we repor ted previously as well as to that of both atrial and ventricular cells from other mammalian species.