CHARACTERISTICS OF TRANSIENT OUTWARD CURRENT IN HUMAN VENTRICULAR MYOCYTES FROM PATIENTS WITH TERMINAL HEART-FAILURE

A variety of outward currents exists in ventricular myocardium of diff erent species influencing action potential duration and electrical act ivity. Transient outward currents have been reported in ventricular ti ssue of some animals but are small or absent in others. This study was conducted to investigate whether a transient outward current exists i n human ventricular myocardium and to characterize its basic electroph ysiological properties. Currents were recorded from enzymatically isol ated human ventricular myocytes obtained from explanted hearts of 22 p atients with terminal heart failure. In almost all cells studied, a tr ansient 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 con ditions in which Ca2+ influx and intracellular Ca2+ transients were su ppressed. Basic current characteristics were similar to transient outw ard 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 wa s 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) account ed 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 in tervention.