Yang Z W, Wang J, Zheng T, Altura B T, Altura B M
Department of Physiology and Pharmacology, Health Science Center at Brooklyn, State University of New York, Brooklyn, New York 11203, USA.
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2898-907. doi: 10.1152/ajpheart.2000.279.6.H2898.
Removal of extracellular Ca(2+) concentration (Ca(2+)) and pretreatment of canine basilar arterial rings with either an antagonist of voltage-gated Ca(2+) channels (verapamil), a selective antagonist of the sarcoplasmic reticulum Ca(2+) pump [thapsigargin (TSG)], caffeine plus a specific antagonist of ryanodine-sensitive Ca(2+) release (ryanodine), or a D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)]- mediated Ca(2+) release antagonist (heparin) markedly attenuates low extracellular Mg(2+) concentration (Mg(2+))-induced contractions. Low Mg(2+)-induced contractions are significantly inhibited by pretreatment of the vessels with Gö-6976 [a protein kinase C-alpha (PKC-alpha)- and PKC-betaI-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(2+) in a concentration-dependent manner. The absence of Ca(2+) and preincubation of the cells with verapamil, TSG, heparin, or caffeine plus ryanodine markedly attenuates the transient and sustained elevations in the intracellular Ca(2+) concentration (Ca(2+)) induced by low-Mg(2+) medium. Low Mg(2+)-produced increases in Ca(2+) are also suppressed markedly in the presence of Gö-6976, Bis, wortmannin, or LY-294002. The present study suggests that both Ca(2+) influx through voltage-gated Ca(2+) channels and Ca(2+) release from intracellular stores [both Ins(1,4,5)P(3) sensitive and ryanodine sensitive] play important roles in low-Mg(2+) medium-induced contractions of isolated canine basilar arteries. Such contractions are clearly associated with activation of PKC isoforms and PI3Ks.
去除细胞外钙离子浓度（Ca(2+)），并用电压门控钙离子通道拮抗剂（维拉帕米）、肌浆网钙离子泵的选择性拮抗剂[毒胡萝卜素（TSG）]、咖啡因加ryanodine敏感钙离子释放的特异性拮抗剂（ryanodine）或D-肌醇1,4,5-三磷酸[Ins(1,4,5)P(3)]介导的钙离子释放拮抗剂（肝素）预处理犬基底动脉环，可显著减弱低细胞外镁离子浓度（Mg(2+)）诱导的收缩。用Gö-6976[一种蛋白激酶C-α（PKC-α）和PKC-βI选择性拮抗剂]、双吲哚马来酰亚胺I（Bis，PKC的特异性拮抗剂）以及渥曼青霉素或LY-294002[磷脂酰肌醇-3激酶（PI3Ks）的选择性拮抗剂]预处理血管，可显著抑制低Mg(2+)诱导的收缩。还发现这些拮抗剂以浓度依赖的方式舒张低Mg(2+)诱导的动脉收缩。去除Ca(2+)以及用维拉帕米、TSG、肝素或咖啡因加ryanodine预孵育细胞，可显著减弱低Mg(2+)培养基诱导的细胞内钙离子浓度（Ca(2+)）的瞬时和持续升高。在存在Gö-6976、Bis、渥曼青霉素或LY-294002的情况下，低Mg(2+)引起的Ca(2+)增加也被显著抑制。本研究表明，通过电压门控钙离子通道的钙离子内流以及细胞内储存库（Ins(1,4,5)P(3)敏感和ryanodine敏感两者）的钙离子释放，在低Mg(2+)培养基诱导的离体犬基底动脉收缩中起重要作用。这种收缩明显与PKC同工型和PI3Ks的激活有关。
