SMOOTH MUSCLE FUNCTION--CELLULAR & MOLECULAR MECHANISMS

该计划项目旨在了解蜂窝和 将刺激与平滑肌收缩联系起来的分子机制。 这个问题将由一个利用这些工具的科学家团队来解决 生物物理学、生理学、分子生物学、生物化学和细胞学 生物学。这项计划的目标将由四个方面来解决 各有不同的项目，并将得到两个核心设施的支持。项目 1的目的是为了了解蛋白激酶C和 钙调素依赖的蛋白激酶II对单个细胞内钙离子的调节 平滑的肌肉细胞。这将通过确定效果来实现 选择性地激活或抑制两者上的特定蛋白激酶 钙进入和钙再吸收过程。项目2有两个 明确的目标：1.确定拉伸背后的离子事件-- 激活的平滑肌收缩；以及，2.测定 自发膜电位背后的离子和代谢事件 震荡。项目3旨在定义结构/活动 平滑肌蛋白激酶C与血管紧张素转换酶的关系 蛋白激酶C和钙调蛋白依赖性蛋白激酶的共同作用 关于负责钙调节的蛋白质(钙泵、钙 通道)。项目4旨在确定变更 在组成收缩装置的分子的组织中 收缩下的平滑肌肉。具体地说， 肌动蛋白、肌球蛋白、钙粘蛋白和钙调蛋白的结构和组织 被调查。这些项目的活动将得到以下方面的支持 一个管理核心和一个生物物理核心提供高级 电生理学、数字成像的仪器和支持 显微镜，笼式可光激活化合物的使用，以及分析 电子显微照片。预计这些项目和核心 将为以下方面提供新的见解：1.离子的作用，第二信使 和蛋白激酶在离子通道调节中的作用；2. 胞质钙的调控和3.细胞内钙激活的机制 收缩机械。

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.