A VOLTAGE-DEPENDENT NORADRENALINE-SENSITIVE INTRACELLULAR CALCIUM STORE IN SMOOTH-MUSCLE CELLS OF THE GUINEA-PIG AORTA

In this study we investigated the effects of K+ depolarization on the contractile responses of guinea-pig aortic smooth muscle to noradrenal ine (NA) and caffeine (CAF) in Ca2+-free Krebs solution (CafKS). NA (1 mu M) or CAF (10 mM) in regular CafKS induced a (termed first) phasic contraction, but responses to a second NA or CAF stimulation were sig nificantly reduced, suggesting a depletion of the common intracellular (NA/CAF sensitive) store previously reported by investigators. After the depletion of this store (i) neither 105 mM KCl CafKS nor 10 mM CAF in this high KC solution induced contraction; (ii) NA-induced contrac tions were enhanced by KCl, increasing dose dependently with KCl rangi ng from 25 to 105 mM; (iii) in 105 mM KCl CafKS repetitive NA stimulat ions elicited enhanced and nondecreasing responses equal to or greater than the first contraction, suggesting an efficient recycling of intr acellular Ca2+. In the presence of 10 mu M cyclopiazonic acid NA-induc ed contraction was enhanced, but the response to a subsequent NA stimu lation in the absence of cyclopiazonic acid was greatly reduced, imply ing an inhibition of the Ca2+ recycling function; (iv) 2.0 mM EGTA (et hylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid) atten uated the NA-induced contractions in regular and 105 mM KCl CafKS. On the basis of the above results we propose that in the smooth muscle ce lls of guinea-pig aorta, there are two intracellular Ca2+ stores: a NA /CAF-sensitive store and a voltage-dependent NA-sensitive store with e ffective Ca2+ recycling capability.