Low [ Mg 2 1 ] o induces contraction and [ Ca 2 1 ] i rises in cerebral arteries : roles of Ca 2 1 , PKC , and PI 3

Yang, Zhi-Wei, Jun Wang, Tao Zheng, Bella T. Altura, and Burton M. Altura. Low [Mg]o induces contraction and [Ca]i rises in cerebral arteries: roles of Ca , PKC, and PI3. Am J Physiol Heart Circ Physiol 279: H2898–H2907, 2000.—Removal of extracellular Ca concentration ([Ca]o) and pretreatment of canine basilar arterial rings with either an antagonist of voltage-gated Ca channels (verapamil), a selective antagonist of the sarcoplasmic reticulum Ca pump [thapsigargin (TSG)], caffeine plus a specific antagonist of ryanodine-sensitive Ca release (ryanodine), or a D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]mediated Ca release antagonist (heparin) markedly attenuates low extracellular Mg concentration ([Mg]o)-induced contractions. Low [Mg]o-induced contractions are significantly inhibited by pretreatment of the vessels with Gö-6976 [a protein kinase C-a (PKC-a)and PKC-bI-selective antagonist], bisindolylmaleimide I (Bis, a specific antagonist of PKC), and wortmannin or LY-294002 [selective antagonists of phosphatidylinositol-3 kinases (PI3Ks)]. These antagonists were also found to relax arterial contractions induced by low [Mg]o in a concentration-dependent manner. The absence of [Ca]o and preincubation of the cells with verapamil, TSG, heparin, or caffeine plus ryanodine markedly attenuates the transient and sustained elevations in the intracellular Ca concentration ([Ca]i) induced by low[Mg]o medium. Low [Mg ]o-produced increases in [Ca ]i are also suppressed markedly in the presence of Gö-6976, Bis, wortmannin, or LY-294002. The present study suggests that both Ca influx through voltage-gated Ca channels and Ca release from intracellular stores [both Ins(1,4,5)P3 sensitive and ryanodine sensitive] play important roles in low-[Mg]o medium-induced contractions of isolated canine basilar arteries. Such contractions are clearly associated with activation of PKC isoforms and PI3Ks.