Stimulation of L-type Ca2+ current by the endothelin receptor A-selective antagonist, BQ-123 in ventricular cardiomyocytes isolated from the rabbit myocardium.
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.
Kelso
E J
EJ
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, Northern Ireland. e.kelso@qub.ac.uk
Spiers
J P
JP
McDermott
B J
BJ
Scholfield
C N
CN
Silke
B
B
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002469:Cell Separation; D004149:Dioxoles / Q000494:pharmacology*; D065128:Endothelin Receptor Antagonists; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011817:Rabbits; D013268:Stimulation, Chemical
D015220:Calcium Channels; D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; C093322:PD 155080; D010456:Peptides, Cyclic; C082887:PD 145065; C072247:cyclo(Trp-Asp-Pro-Val-Leu)