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Am J Physiol Heart Circ Physiol 279: H2898-H2907, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 6, H2898-H2907, December 2000

Low [Mg2+]o induces contraction and [Ca2+]i rises in cerebral arteries: roles of Ca2+, PKC, and PI3

Zhi-Wei Yang1, Jun Wang2, Tao Zheng1, Bella T. Altura1,4, and Burton M. Altura1,3,4

Departments of 1 Physiology and Pharmacology, 2 Anesthesiology, and 3 Medicine, and 4 Center for Cardiovascular and Muscle Research, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 11203

Removal of extracellular Ca2+ concentration ([Ca2+]o) and pretreatment of canine basilar arterial rings with either an antagonist of voltage-gated Ca2+ channels (verapamil), a selective antagonist of the sarcoplasmic reticulum Ca2+ pump [thapsigargin (TSG)], caffeine plus a specific antagonist of ryanodine-sensitive Ca2+ release (ryanodine), or a D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]- mediated Ca2+ release antagonist (heparin) markedly attenuates low extracellular Mg2+ concentration ([Mg2+]o)-induced contractions. Low [Mg2+]o-induced contractions are significantly inhibited by pretreatment of the vessels with Gö-6976 [a protein kinase C-alpha (PKC-alpha )- and PKC-beta I-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 [Mg2+]o in a concentration-dependent manner. The absence of [Ca2+]o and preincubation of the cells with verapamil, TSG, heparin, or caffeine plus ryanodine markedly attenuates the transient and sustained elevations in the intracellular Ca2+ concentration ([Ca2+]i) induced by low-[Mg2+]o medium. Low [Mg2+]o-produced increases in [Ca2+]i are also suppressed markedly in the presence of Gö-6976, Bis, wortmannin, or LY-294002. The present study suggests that both Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from intracellular stores [both Ins(1,4,5)P3 sensitive and ryanodine sensitive] play important roles in low-[Mg2+]o medium-induced contractions of isolated canine basilar arteries. Such contractions are clearly associated with activation of PKC isoforms and PI3Ks.

canine basilar arteries; extracellular magnesium concentration deficiency; calcium influx; intracellular calcium release; protein kinase C; phosphatidylinositol-3 kinase


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