Characterization of effects of endothelin-1 on the L-type Ca2+ current in human atrial myocytes

Abstract

The effects of endothelin-1 (ET-1) on the L-type Ca2+ current ( I Ca) were examined in whole cell patch-clamped human atrial myocytes. Depending on the initial current density, ET-1 (10 nM) increased the amplitude of I Ca by 99 ± 7% or decreased it by 33 ± 2%. The stimulatory effect predominated on current of low density (2.3 ± 0.2 pA/pF), whereas I Ca of higher density (5.8 ± 0.3 pA/pF) was inhibited by ET-1. After I Castimulation by 1 μM isoproterenol, ET-1 always inhibited the current by 32 ± 7% ( P < 0.05), an effect that was suppressed by pretreating myocytes with pertussis toxin. Atrial natriuretic peptide (ANP) inhibited I Ca (41 ± 3%) by reducing intracellular cAMP concentration. In ANP-treated myocytes, the stimulatory effect of ET-1 on I Capredominated (52 ± 7%). The inhibitory effect of ET-1 on I Ca was blocked by the ETAantagonist BQ-123, whereas the stimulatory effect was suppressed by the ETB agonist BQ-788. We conclude that ET-1 has opposite effects on I Ca depending on the baseline amplitude of current, and both subtype ET receptors are implicated in the signal transduction pathways.