STIMULATION OF L-TYPE CA2-SELECTIVE ANTAGONIST, BQ-123, IN VENTRICULAR CARDIOMYOCYTES ISOLATED FROM RABBIT MYOCARDIUM( CURRENT BY THE ENDOTHELIN RECEPTOR A)

BQ-123 is extensively used as an antagonist at endothelin (ET) recepto rs, having selectivity at the ETA, receptor subtype. In this study, th e effects of BQ-123 per se on action potentials, L-type calcium curren ts, and potassium currents, were examined in Ventricular cardiomyocyte s isolated from adult, male, New Zealand White rabbits, using the patc h-clamp technique. BQ-123 (1 mu M) increased (P < 0.02) the duration o f 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 tran sient 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 Ca 2+ 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, B Q-788, PD155080 and PD145065 (1-10 mu M) did not affect the L-type Ca2 + current. These results indicate that, unlike PD155080, BQ-788 and PD 145065, the conventional ETA, receptor-selective antagonist, BQ-123, e xerts a unique positive effect on the L-type Ca2+ current in ventricul ar cardiomyocytes isolated from rabbit myocardium. The mechanism of ac tion of BQ-123, therefore, is not confined to ET receptor antagonism. (C) 1998 Elsevier Science Inc.