Effects of RP58866 on transmembrane K + currents in mammalian ventricular myocytes

Abstract

AIM: To determine effects of RP58866 on inward rectifier K + current (I(Kl)), transient outward K + current (I(to)) and delayed outward rectifier K + current (I(K)) in isolated cardiac myocytes. METHODS: In isolated ventricular myocytes of guinea pig and dog, the effect of RP58866 on I(Kl), I(to), and I(K) were observed by the whole cell voltage-clamp technique. RESULTS: RP58866 decreased I(Kl) in a concentration-dependent manner, with an IC 50 of (3.4 ± 0.8) μmol · L -1 (n = 6) at -100 mV in guinea pig ventricular cells. In dog ventricular myocytes, RP58866 inhibited I(to) with IC 50 of (2.3 ± 0.5) μmol · L -1 at +40 mV. In guinea pig ventricular cells, RP58866 at 100 μmol · L -1 decreased I(K): I(Kstep) by (58 ± 13)% at +40 mV, and I(Ktail) by (86 ± 17)%, respectively. RP58866 inhibited I(Kstep) with an IC 50 of (7.5 ± 0.8) μmol · L -1, and I(Ktail) with an IC 50 of (3.5 ± 0.9) μmol · L -1. The envelope of tail analysis suggested that both I(Kr) and I(Ks) were inhibited. CONCLUSION: RP58866 inhibits I(Kl), I(to), and I(K) in cardiac myocytes with a similar potency, and is not a specific I(Kl) inhibitor.