ADRENERGIC REGULATION OF CARDIAC MUSCLE CONTRACTION

拟议研究的长期目标是阐明 激动剂与肌醇磷脂连接的分子机制 新陈代谢改变哺乳动物心脏的收缩能力。一个关键假说 要测试的是α-肾上腺素能、Kappa-阿片和内皮素-1 受体偶联到特定的二酰甘油途径 升高，导致蛋白激酶C选择性激活 与此相关的特定蛋白的异构体和磷酸化 收缩装置。磷酸化对细胞外信号转移率的影响 活化和松弛以及产物释放的动力学 跨桥周期中的步骤将使用该小说进行检查 笼状化合物的脉冲光解快速改变钙离子的方法， 单个心肌细胞中的无机磷和ADP。信息 这将为了解心脏疾病的变化提供依据。 在心力衰竭、缺血/再灌注损伤期间或在 慢性疾病状态，如高血压或糖尿病。

The long range goals of the proposed research are to elucidate the molecular mechanisms by which agonists linked to phosphoinositide metabolism alter contractility of the mammalian heart. A key hypothesis to be tested is that alpha-adrenergic, Kappa-opioid and endothelin-1 receptors are coupled to pathways in which specific diacylglycerols become elevated, leading to selective activation of protein kinase C isoforms and phosphorylation of specific proteins associated with the contractile apparatus. The effects of phosphorylation on rates of activation and relaxation, as well as on the kinetics of product release steps during the cross-bridge cycle will be examined using the novel method of pulse photolysis of caged compounds to rapidly alter Ca2+, inorganic phosphate and ADP in single cardiac myocytes. Information obtained will provide a basis for understanding changes in cardiac performance during heart failure, ischemic/reperfusion injury or during chronic diseased states such as hypertension or diabetes.