CAPACITATIVE CA2-ADRENOCEPTORS IN RAT AORTA( ENTRY ASSOCIATED WITH ALPHA(1))

In rat aorta, depletion of internal Ca2+ stores by addition of noradre naline (1 mu M) induces a biphasic response (an initial phasic respons e and a tonic one) mediated by two different intracellular Ca2+ pools. This response cannot be repeated, suggesting a depletion of internal Ca2+ stores sensitive to noradrenaline. In absence of the agonist, thi s depletion is the signal for the entry of extracellular Ca2+, not onl y to refill the stores but also, under our experimental conditions, to activate the contractile proteins thus inducing an increase in the re sting tone (IRT) that constitutes functional evidence of this Ca2+ ent ry. The ionic channels involved in the mechanism of the IRT have been studied in the present work. The fact that the addition of nimodipine (10(-15) 10(-11) M) selectively inhibits the IRT suggests that this me chanical response is mediated by Ca2+ influx through dihydropyridine-s ensitive Ca2+ channels. Moreover, the inhibitory action of nimodipine is attenuated by glibenclamide (10 mu M). Cromakalim (10(-10)-10(-6) M ) also inhibits the IRT concentration dependently, and this inhibition is antagonized by glibenclamide (10 mu M). These results relate the A TP-dependent K+ channels to the mechanism of the IRT. The refilling of the two internal Ca2+ compartments sensitive to noradrenaline was, li ke the IRT, altered in presence of the compounds tested, since the sub sequent contractile response to noradrenaline was decreased. The prese nt results suggest that nimodipine treatment inhibits the refilling of the Ca2+ compartment responsible for the tonic contraction induced by noradrenaline in Ca2+-free medium, whereas the refilling of the Ca2pool responsible for the phasic response to noradrenaline remained una ltered. Both the phasic and tonic responses to noradrenaline in Ca2+-f ree medium decreased after treatment with cromakalim. We can therefore assume that the refilling of both Ca2+ compartments sensitive to nora drenaline was inhibited. In conclusion, these results are consistent w ith the contraction of the rat aorta in response to noradrenaline in C a2+-free medium consisting of an initial phasic response and a tonic o ne. The former is due to the release of internal Ca2+ from a compartme nt refilled through a special channel that is cromakalim but not dihyd ropyridine sensitive. The tonic response is due to Ca2+ release from a nother compartment refilled through a cromakalim- and dihydropyridine- sensitive Ca2+ channel. The Ca2+ entry through this latter channel int ervenes in the IRT observed during the refilling of these stores previ ously depleted by noradrenaline, and the opening state of this channel is also modulated by ATP-dependent K2+ channels.