MECHANISMS AND THERAPY OF CIRCULATORY DISEASE

循环系统疾病的机制和治疗

• 批准号: 3097389
• 负责人: DAVID R HATHAWAY
• 金额: $ 89.98万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-03-01 至 1993-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097389
• 关键词: heart metabolism; phosphorylation; vascular smooth muscle

The overall goal of this Program Project is to generate basic knowledge concerning fundamental cellular mechanisms that mediate the normal intracellular environment essential for coordinated electrical and contractile function in heart and blood vessels. A unifying subtheme selected for this competitive renewal is Ca2+ ions and protein phosphorylation - interacting subcellular mechanisms of regulation in cardiac and vascular muscle. The broad specific aims that will be pursued through interactive and collaborative studies are: 1) to delineate key molecular mechanisms that account for the unique roles of the cholinergic and adrenergic limbs of the autonomic nervous system in regulating electrical and/or contractile function of cardiac and vascular muscle, 2) to identify and characterize pivotal protein kinase and/or phosphatase systems that commonly affect muscle electrophysiology or contractility through direct action on ion pumps, antiporters, channels or contractile and regulatory proteins, 3) to isolate and define the interaction of contractile and regulatory protein complexes that account for the unique force maintenance mechanism in vascular smooth muscle, a process that is dependent upon both Ca2+ and protein phosphorylation, and 4) to study specific ion channels, antiporters, or pump systems at the cellular and membrane level, elucidate specific molecular mechanisms of regulation and investigate interactions of these mechanisms at the intact tissue level. A variety of preparations or methodologies will be utilized in order to pursue the specific aims including cellular microelectrodes, perfused hearts, isolated cardiac myocytes, cultured cells, planar lipid bilayers, protein purification, monoclonal antibodies, protein sequencing, muscle mechanics, and recombinant DNA. This Program Project will produce a body of information that can serve as a logical paradigm for subsequent study of disease states such as cardiac arrhythmia and atherosclerosis.

该项目的总体目标是产生基本的 关于基本细胞机制的知识， 正常的细胞内环境对于协调 心脏和血管的电和收缩功能。 为这种竞争性更新选择的一个统一的子主题是Ca 2 + 离子与蛋白质磷酸化相互作用 心脏和血管肌肉的调节机制。 广大 将通过互动和 合作研究是：1）描绘关键分子 解释胆碱能和神经递质的独特作用的机制， 自主神经系统的肾上腺素能分支在调节 心脏和血管的电和/或收缩功能 肌肉，2）鉴定和表征关键蛋白激酶 和/或通常影响肌肉的磷酸酶系统 通过直接作用于离子的电生理学或收缩性 泵、反向转运体、通道或收缩和调节 蛋白质，3）分离和定义收缩的相互作用， 和调节蛋白复合物， 维持机制在血管平滑肌，这是一个过程， 依赖于Ca 2+和蛋白质磷酸化，以及4） 研究特定的离子通道，反向转运蛋白，或泵系统在 细胞和膜水平，阐明特定分子 调节机制，并研究这些相互作用 在完整组织水平的机制。 各种准备工作 或方法将被用来追求具体的 目的包括细胞微电极，灌注心脏，离体 心肌细胞，培养细胞，平面脂双层，蛋白质 纯化，单克隆抗体，蛋白质测序，肌肉 力学和重组DNA 该项目将产生 可以作为逻辑范例的信息体， 随后对心律失常等疾病状态的研究， 动脉粥样硬化