Characteristics of transient outward current in human ventricular myocytes from patients with terminal heart failure

Abstract

A variety of outward currents exists in ventricular myocardium of different species influencing action potential duration and electrical activity. Transient outward currents have been reported in ventricular tissue of some animals but are small or absent in others. This study was conducted to investigate whether a transient outward current exists in human ventricular myocardium and to characterize its basic electrophysiological properties. Currents were recorded from enzymatically isolated human ventricular myocytes obtained from explanted hearts of 22 patients with terminal heart failure. In almost all cells studied, a transient outward current could be recorded on depolarization to between -20 and +80 mV. The size of the transient outward current was usually large enough to mask the Ca2+ current. It could be recorded under conditions in which Ca2+ influx and intracellular Ca2+ transients were suppressed. Basic current characteristics were similar to transient outward currents observed in other species. Inactivation of the transient outward current was monoexponential, with a time constant of 54.8±3.7 milliseconds at +40 mV. Half-maximal activation occurred at 16.7±1.6 mV; half-maximal steady-state inactivation occurred at -34.5±2.3 mV. Frequency-dependent reduction of peak transient outward current was 29.8±1.4% at 2 Hz compared with resting conditions. Recovery from inactivation was voltage dependent and had a biexponential time course; the faster time constant (41.0±6.5 milliseconds at -80 mV) accounted for 86.0±5.2% of total current. The transient outward current was sensitive to 4-aminopyridine (IC50, 1.15 mM). These results indicate that a large Ca2+-independent transient outward K+ current is present in human ventricular myocytes that might be regulated by physiological or pathological events and is a potential site for pharmacological intervention.