It has been suggested that the positive inotropic effect of the vasoactive peptide hormone, endothelin-1 (ET-1), involves inhibition of cardiac K+ currents. In order to identify the K+ currents modulated by ET-I, the outward K+ currents of isolated rat ventricular myocytes were investigated using whole-cell patch-clamp recording techniques. Outward currents were elicited by depolarisation to +40 mV for 200 ms from the holding potential of -60 mV, Currents activated rapidly, reaching a peak (I-pk) Of 1310 +/- 115 PA and subsequently inactivating to an outward current level of 1063 +/- 122 PA at the end of the voltage-pulse (I-late) (n = II). ET-I (20 nM) reduced I-pk by 247.6 +/-60 7 PA (n = II, P < 0.01) and reduced I-late by 323.2 +/- 43.9 pA (P < 0.001). The effects of ET-1 were abolished in the presence of the nonselective ET receptor antagonist, PD 142893 (10 muM, n = 5). Outward currents were considerably reduced and the effects of ET-I were not observed when K+ was replaced with Cs+ in the experimental solutions; this indicates that ET-I modulated K+-selective currents. a double-pulse protocol was used to investigate the inactivation of the currents. The voltage-dependent inactivation of the currents from potentials positive to -80 mV was fitted by a Boltzmann equation revealing the existence of an inactivating transient outward component (I-to) and a noninactivating steady-state component (I-ss), ET-1 markedly inhibited I-ss by 43.0 +/- 3.8% (P < 0.001, n = 7) and shifted the voltage-dependent inactivation of I-to by +3.3 +/- 1.2 mV (P < 0.05). Although ET-I had little effect on the onset of inactivation of the currents elicited from a conditioning potential of -70 mV, the time-independent noninactivating component of the currents was markedly inhibited. In conclusion, the predominant effect of ET-1 was to inhibit a noninactivating steady-state background K+ current (I-ss). These results are consistent with the hypothesis that I-ss inhibition contributes to the inotropic effects of ET-I,