Evidence for two separated Ca2+ pathways in smooth muscle plasmalemma.

The activation of rabbit aortic smooth muscle was studied by two most widely used vascular smooth muscle stimulants: alpha-adrenoceptor activation by norepinephrine (NE) and high-K+ depolarization. This was studied by measurements of isometric contractions and net as well as unidirectional Ca2+ fluxes. These parameters showed markedly differential sensitivities towards tow smooth muscle inhibitors used in this study: D600 and amrinone. By choosing an appropriate concentration of D600 or amrinone, Ca2+ uptake or Ca2+ influx induced by high K+ or NE could by selectively inhibited. Furthermore, by using unidirectional flux measurements it was demonstrated that Ca2+ influx stimulated by NE and high K+ were additive in nature. The data from the addivity experiment exclude the interpretation of a common Ca2+ pathway with two separate mechanisms for opening it. The data on three criteria employed in this study provide evidence for the existence of two independent Ca2+ pathways, one for each mode of activation, for Ca2+ influx known to be associated with these contractions.