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

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-Ca stimulation by 1 muM 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-Ca predominated (52 +/- 7%). The inhibitory effect of ET-1 on I-Ca was blocked by the ETA antagonist 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.