REGULATION OF L-TYPE CA++ CHANNEL IN SMOOTH MUSCLE CELLS

本项目将验证以下假设：1)G蛋白通过cAMP/PK-A途径激活VSM L型钙通道；2)cGMP可能通过磷酸化钙通道或一些调节蛋白而对这些钙通道起抑制作用。这些假说将通过利用新鲜分离的门静脉肌细胞、瞬时表达的VSM L型钙亚基、纯化的G蛋白亚基和各种非特异性和特异性蛋白激酶阻滞剂来评估。该项目的结果将提供G蛋白和蛋白激酶在生理刺激后调节VSM细胞内钙进入的细胞事件，以诱导血管扩张和血管收缩。钙通道是许多用于治疗高血压的药物的靶点，如二氢吡啶、肾上腺素能激动剂和拮抗剂。通过进一步明确调节钙离子进入的信号转导通路，可以开发控制高血压的新策略。

This project will test the hypotheses that 1) G protein activates VSM L-type Ca2+ channels via cAMP/PK-A pathway, and 2) cGMP may exerts its inhibitory effect on these Ca2+ channels via phosphorylation of Ca2+ channels or some regulatory proteins by PKG. These hypotheses will be evaluated by utilizing freshly isolated portal vein myocytes, transiently expressed VSM L-type Ca2+ subunits, purified G protein subunits, and variety of non- specific and specific protein kinase blockers. Results from this project will provide cellular events by which G proteins and protein kinases regulate Ca2+ entry in VSM cells following physiological stimulation to induce vasodilation and vasoconstriction. Ca2+ channels are targets for a number of 2drugs used in the treatment of hypertension such as dihydropyridines, and adrenergic agonists and antagonists. By further defining the signal transduction pathways regulating Ca2+ entry, new strategies could be developed to control high blood pressure.