Role of iPLA2 and store-operated channels in agonist-induced Ca influx and constriction in cerebral, mesenteric, and carotid arteries

Park KM, Trucillo M, Serban N, Cohen RA, Bolotina VM. Role of iPLA2 and store-operated channels in agonist-induced Ca influx and constriction in cerebral, mesenteric, and carotid arteries. Am J Physiol Heart Circ Physiol 294: H1183–H1187, 2008. First published December 21, 2007; doi:10.1152/ajpheart.01148.2007.—Store-operated channels (SOC) and store-operated Ca entry are known to play a major role in agonist-induced constriction of smooth muscle cells (SMC) in conduit vessels. In microvessels the role of SOC remains uncertain, in as much as voltage-gated L-type Ca (CaL 2 ) channels are thought to be fully responsible for agonist-induced Ca influx and vasoconstriction. We present evidence that SOC and their activation via a Ca -independent phospholipase A2 (iPLA2)-mediated pathway play a crucial role in agonist-induced constriction of cerebral, mesenteric, and carotid arteries. Intracellular Ca in SMC and intraluminal diameter were measured simultaneously in intact pressurized vessels in vitro. We demonstrated that 1) Ca and contractile responses to phenylephrine (PE) in cerebral and carotid arteries were equally abolished by nimodipine (a CaL 2 inhibitor) and 2-aminoethyl diphenylborinate (an inhibitor of SOC), suggesting that SOC and CaL 2 channels may be involved in agonist-induced constriction of cerebral arteries, and 2) functional inhibition of iPLA2 totally inhibited PE-induced Ca influx and constriction in cerebral, mesenteric, and carotid arteries, whereas K -induced Ca influx and vasoconstriction mediated by CaL 2 channels were not affected. Thus iPLA2-dependent activation of SOC is crucial for agonistinduced Ca influx and vasoconstriction in cerebral, mesenteric, and carotid arteries. We propose that, on PE-induced depletion of Ca stores, nonselective SOC are activated via an iPLA2-dependent pathway and may produce a depolarization of SMC, which could trigger a secondary activation of CaL 2 channels and lead to Ca entry and vasoconstriction.