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: 2767598
• 负责人: JUMING ZHONG
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-04 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2767598
• 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.

本课题将验证以下假说：1）G蛋白通过cAMP/PK-A途径激活VSM L型Ca~（2+）通道; 2）cGMP可能通过PKG磷酸化Ca~（2+）通道或某些调节蛋白而对这些Ca~（2+）通道发挥抑制作用。 这些假设将通过使用新鲜分离的门静脉肌细胞、瞬时表达的VSM L型Ca2+亚单位、纯化的G蛋白亚单位以及各种非特异性和特异性蛋白激酶阻断剂进行评价。 该项目的结果将提供细胞事件，G蛋白和蛋白激酶通过这些事件调节生理刺激后VSM细胞中的Ca 2+进入，以诱导血管舒张和血管收缩。 钙离子通道是二氢吡啶类药物、肾上腺素能激动剂和拮抗剂等治疗高血压药物的靶点。 通过进一步确定调节Ca2+内流的信号转导途径，可以开发新的策略来控制高血压。