INHIBITION OF VOLTAGE-DEPENDENT CA2+-CURRENT BY ALPHA-ADRENOCEPTOR AGONISTS IN SMOOTH-MUSCLE CELLS

The cellular mechanisms underlying the inhibitory effects of phenylephrine on dihydropyridine-sensitive, voltage-dependent Ca2+ currents recorded from single smooth muscle cells dissociated from the rat anococcygeus muscle were examined. Phenylephrine (0.1-30 mu M) produced a concentration-dependent inhibition of the Ca2+ current; the maximum response occured at a concentration of 10 mu M, which inhibited the peak inward current evoked at 0 mV by 57.7 +/- 4% (n = 8). The response to phenylephrine was reduced but not abolished in cells containing 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), and it persisted in cells dialysed internally with heparin (5 mg . ml(-1)). This was despite the fact that both EGTA (5 mM) and heparin were able to block the phenylephrine-induced, Ca2+-dependent chloride current recorded in the same cells. The inhibition of the Ca2+ current produced by phenylephrine was abolished in cells containing guanosine 5'-[beta-thio]diphosphate (GDP-beta-S) but persisted in cells pre-treated with pertussis toxin. Our results suggest that the inhibition of L-type Ca2+ current seen following alpha-adrenoceptor activation occurs by a mechanism independent from the inositol trisphosphate-mediated release of Ca2+ from intracellular stores.