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

AIM: To determine effects of RP58866 on inward rectifier K+ current (I-K1), transient outward K+ current (I-K1) and delayed outward rectifier K+ curre nt (I-K) in isolated cardiac myocytes. METHODS: In isolated ventricular myo cytes of guinea pig and dog, the effect of RP58866 on I-K1, I-to, and I-K w ere observed by the whole cell voltage-clamp technique. RESULTS: RP58866 de creased I-K1 in a concentration-dependent manner, with an IC50 Of (3.4 +/- 0.8) mu mol.L-1(n = 6) at - 100 mV in guinea pig ventricular cells. In dog ventricular myocytes, RP58866 inhibited I-to,with IC50 of (2.3 +/- 0.5) mu mol.L-1 at + 40 mV. In guinea pig ventricular cells, RP58866 at 100 mu mol. 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 IC50 of (7.5 +/- 0.8) mu mol.L-1, and I-Ktail with an IC50 Of (3.5 +/- 0.9) mu mol L-1. The envelope of tail analysis suggested that both I-Kr and I-Ks were inhibited . CONCLUSION: RP58866 inhibits I-K1, I-to, and I-K in cardiac myocytes with a similar potency, and is not a specific I-K1 inhibitor.