Stimulation of L-type Ca2+ current by the endothelin receptor A-selective antagonist, BQ-123 in ventricular cardiomyocytes isolated from the rabbit myocardium

Biochem Pharmacol. 1998 Mar 15;55(6):897-902. doi: 10.1016/s0006-2952(97)00581-9.

Abstract

BQ-123 is extensively used as an antagonist at endothelin (ET) receptors, having selectivity at the ET(A) receptor subtype. In this study, the effects of BQ-123 per se on action potentials, L-type calcium currents, and potassium currents, were examined in ventricular cardiomyocytes isolated from adult, male, New Zealand White rabbits, using the patch-clamp technique. BQ-123 (1 microM) increased (P < 0.02) the duration of the action potential to 267 +/- 36 ms from a control duration of 228 +/- 30 ms. BQ-123 did not have any effect on the inward rectifier or transient outward potassium currents, but increased (P < 0.02) the L-type Ca2+ current to -2.76 +/- 0.3 nA from a control value of -2.45 +/- 0.28 nA. The increases in both duration of the action potential and L-type Ca2+ current were reversed upon washout (233 +/- 28 ms and -2.32 +/- 0.31 nA, respectively) and were not different from the control values in the absence of BQ-123. In contrast, the endothelin receptor antagonists, BQ-788, PD155080 and PD145065 (1-10 microM) did not affect the L-type Ca2+ current. These results indicate that, unlike PD155080, BQ-788 and PD145065, the conventional ET(A) receptor-selective antagonist, BQ-123, exerts a unique positive effect on the L-type Ca2+ current in ventricular cardiomyocytes isolated from rabbit myocardium. The mechanism of action of BQ-123, therefore, is not confined to ET receptor antagonism.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Calcium Channels / drug effects*
  • Cell Separation
  • Dioxoles / pharmacology*
  • Endothelin Receptor Antagonists*
  • Heart Ventricles / cytology
  • Heart Ventricles / drug effects*
  • Male
  • Oligopeptides / pharmacology*
  • Patch-Clamp Techniques
  • Peptides, Cyclic / pharmacology*
  • Rabbits
  • Stimulation, Chemical

Substances

  • Calcium Channels
  • Dioxoles
  • Endothelin Receptor Antagonists
  • Oligopeptides
  • PD 155080
  • Peptides, Cyclic
  • PD 145065
  • cyclo(Trp-Asp-Pro-Val-Leu)