Inability of endothelin to increase Ca2+ current in guinea-pig heart cells.

Effects of endothelin, a novel vasoconstrictor peptide derived from vascular endothelial cells, on cardiac contractility and membrane currents, were examined in guinea-pig cardiac preparations. Endothelin (3-1000 nM) produced a positive inotropic effect in papillary muscles in a concentration-dependent manner. In whole-cell voltage clamp recording, endothelin (250 nM) decreased the amplitude of Ca2+ current (ICa, 25.0 +/- 6.6%) in ventricular myocytes. The endothelin-induced decrease in ICa was abolished by pretreatment with ryanodine (1 microM). These results suggest that endothelin does not activate cardiac sarcolemmal Ca2+ channels. The enhancement of the sarcoplasmic reticulum function may play an important role in the positive inotropic effect of endothelin.