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

平滑肌细胞 L 型 CA 通道的调节

• 批准号: 6164988
• 负责人: JUMING ZHONG
• 金额: $ 1.43万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6164988
• 关键词: G protein; biological signal transduction; cGMP dependent protein kinase; calcium channel; cyclic GMP; laboratory rabbit; protein kinase A; tissue /cell culture; transfection; vascular smooth muscle; voltage /patch clamp

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.

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Ca2+通道，2)cGMP可能通过PKG磷酸化Ca2+通道或一些调节蛋白对这些Ca2+通道发挥抑制作用。这些假设将通过新分离的门静脉肌细胞、瞬时表达的VSM l型Ca2+亚基、纯化的G蛋白亚基以及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Ca2+进入以诱导血管舒张和血管收缩的细胞事件。Ca2+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。通过进一步确定调节Ca2+进入的信号转导途径，可以开发出控制高血压的新策略。