SMOOTH MUSCLE FUNCTION--CELLULAR & MOLECULAR MECHANISMS

平滑肌功能——细胞

• 批准号: 2223730
• 负责人: FREDRIC S FAY
• 金额: $ 138.34万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223730
• 关键词: muscle function; smooth muscle

This program project is directed at understanding the cellular and molecular mechanisms linking stimulation to contraction of smooth muscle. This issue will be addressed by a team of scientists utilizing the tools of Biophysics, Physiology, Molecular Biology, Biochemistry, and Cell Biology. The objective of this program will be addressed by four distinct projects and will be supported by two core facilities. Project 1 is directed at understanding the role of protein kinase C and calmodulin-dependent protein kinase II in regulating [Ca2+] within single smooth muscle cells. This will be accomplished by determining the effect of selectively activating or inhibiting specific protein kinases on both calcium entry and calcium re-uptake processes. Project 2 has two distinct aims: 1. Determination of the ionic events underlying stretch- activated contraction of smooth muscle; and, 2. Determination of the ionic and metabolic events underlying spontaneous membrane potential oscillations. Project 3 is directed at defining the structure/activity relationship of smooth muscle protein kinase C and in determining the effect of both protein kinase C and calmodulin-dependent protein kinase II on proteins responsible for calcium regulation (calcium pumps, calcium channels) in smooth muscle. Project 4 is directed at determining changes in the organization of molecules that comprise the contractile apparatus of smooth muscle underlying contraction. Specifically, changes in the structure and organization of actin, myosin, calponin, and caldesmon will be investigated. The activities in these projects will be supported by an Administrative Core and a Biophysics Core providing advanced instrumentation and support for electrophysiology, digital imaging microscopy, the use of caged photoactivatable compounds, and the analysis of electron micrographs. It is anticipated that these projects and cores will provide new insights into: 1. The role of ions, second messengers and protein kinases in the regulation of ion channels; 2. Mechanisms of control of cytoplasmic calcium and 3. Mechanisms of activation of the contractile machinery.

该程序项目旨在了解细胞和 将刺激与平滑肌收缩联系起来的分子机制。 一个科学家团队利用工具将解决这个问题 生物物理学，生理学，分子生物学，生物化学和细胞 生物学。 该计划的目的将由四个 不同的项目，并将得到两个核心设施的支持。 项目 1致力于了解蛋白激酶C和 钙调蛋白依赖性蛋白激酶II在调节单个内部[Ca2+]中 平滑肌细胞。 这将通过确定效果来实现 在两者上有选择地激活或抑制特异性蛋白激酶 钙进入和钙的再摄取过程。 项目2有两个 不同的目的：1。确定伸展的离子事件的确定 平滑肌的激活收缩； 2。确定 离子和代谢事件的自发膜电势 振荡。 项目3旨在定义结构/活动 平滑肌蛋白激酶C的关系以及确定 蛋白激酶C和钙调蛋白依赖性蛋白激酶的影响 II负责钙调节的蛋白质（钙泵，钙 通道）平滑肌。 项目4致力于确定更改 在构成收缩设备的分子的组织中 平滑肌的基础收缩。 具体而言，变化 肌动蛋白，肌球蛋白，calponin和Caldesmon的结构和组织将 被调查。 这些项目中的活动将得到 提供高级的行政核心和生物物理核心 仪器和对电生理学，数字成像的支持 显微镜，笼中光活化化合物的使用和分析 电子显微照片。 预计这些项目和核心 将提供新的见解：1。离子，第二使者的作用 在离子通道调节中的蛋白激酶； 2。机制 控制细胞质钙和3。 收缩机械。