MECHANISMS AND THERAPY OF CIRCULATORY DISEASE

循环系统疾病的机制和治疗

• 批准号: 3097390
• 负责人: DAVID R HATHAWAY
• 金额: $ 83.91万
• 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 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097390
• 关键词: heart metabolism; membrane channels; membrane transport proteins; 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.

该计划项目的总体目标是产生基本的 有关介导的基本细胞机制的知识 正常的细胞内环境对于协调至关重要 心脏和血管的电和收缩功能。 此次竞争性更新选择的统一子主题是 Ca2+ 离子和蛋白质磷酸化 - 相互作用的亚细胞 心肌和血管肌肉的调节机制。 广义的 将通过互动和交流来实现的具体目标 合作研究是：1）描绘关键分子 解释胆碱能和胆碱能独特作用的机制 肾上腺素能肢体对自主神经系统的调节作用 心脏和血管的电和/或收缩功能 肌肉，2) 识别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、逆向转运蛋白、通道或收缩和调节 蛋白质，3）分离和定义收缩的相互作用 和调节蛋白复合物具有独特的力量 血管平滑肌的维持机制，这个过程是 依赖于 Ca2+ 和蛋白质磷酸化，4) 研究特定离子通道、反向转运蛋白或泵系统 细胞和膜水平，阐明特定分子 调节机制并研究它们之间的相互作用 完整组织水平的机制。 各种准备工作 或将利用方法来追求具体的 目标包括细胞微电极、灌注心脏、分离 心肌细胞、培养细胞、平面脂质双层、蛋白质 纯化、单克隆抗体、蛋白质测序、肌肉 力学和重组DNA。 该计划项目将产生 可以作为逻辑范式的信息体 随后对心律失常等疾病状态的研究 动脉粥样硬化。