ADRENERGIC REGULATION OF CARDIAC MUSCLE CONTRACTION

拟议研究的长期目标是阐明 与磷酸肌醇连接的激动剂的分子机制 代谢改变哺乳动物心脏的收缩性。 一个关键假设 α-肾上腺素能，κ-阿片类和内皮素-1 受体与特定的甘油二酯 升高，导致蛋白激酶C的选择性激活 同种型和磷酸化的特定蛋白质相关的 收缩器 磷酸化对细胞凋亡率的影响 激活和松弛，以及对产品释放的动力学 跨桥周期的步骤将使用新的 脉冲光解笼状化合物以快速改变Ca 2+的方法， 无机磷和ADP。 信息 获得的结果将为了解心脏的变化提供基础。 心力衰竭、缺血/再灌注损伤或 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.