Modulation of Ca2+ transients in neonatal and adult rat cardiomyocytes by endothelin-1.

Endothelin-1 (ET-1) may exert inotropic and chronotropic effects in cardiac muscle by modulating intracellular Ca2+. This study assesses effects of ET-1 on intracellular free Ca2+ concentration ([Ca2+]i) in neonatal and adult rat cardiomyocytes. [Ca2+]i was measured by Fura 2 methodology. ET receptor subtypes were determined by binding studies. ET-1 increased neonatal and adult [Ca2+]i and spike frequency in a dose-dependent manner. It decreased [Ca2+]i amplitude in neonatal cardiomyocytes but had no effect on [Ca2+]i amplitude in adult cells. The ET(A) receptor antagonist BQ-123 reduced ET-1-induced responses and the ETB receptor agonist IRL-1620 increased [Ca2+]i. ET-1 binding studies demonstrated 85% displacement by BQ-123 and 15% by the ETB receptor agonist sarafotoxin S6c, suggesting a predominance of ET(A) receptors. These data demonstrate that in neonatal and adult cardiomyocytes ET-1 has stimulatory effects on [Ca2+]i which are mediated predominantly via ET(A) receptors. Therefore, ET-1 may influence cardiac development and function.