Endothelin-A receptor mediates cardiac inhibition by regulating calcium and potassium currents

摘要: Voltage-sensitive ion channels play fundamental roles in the regulation of cardiac function by various neurotransmitters. Endothelins have strong positive inotropic and chronotropic effects, for which recent studies implicated intracellular mechanisms. However, very little is known about underlying ion-channel peptide. We report here that endothelin-1 consistently hyperpolarizes membrane shortens duration action potential mammalian atrial myocytes, leading to suppression electrical excitability heart. Endothelin-1, but not endothelin-3, inhibited L-type calcium current decreasing cyclic AMP accumulation activated muscarinic potassium stimulating a pertussis toxin-sensitive GTP-binding protein. Consistent with these results, strongly reduced heart rate when it was increased beta-adrenoceptor stimulation. These effects were blocked an ETA (endothelin-1-selective) receptor-selective antagonist, BQ123 (refs 8-11). The receptor-mediated gives new insight into our understanding physiological pathophysiological endothelins control function.