ELECTROPHYSIOLOGIC PROPERTIES OF ENTOTHELIAL CELLS

拟议研究的长期目标是提供更好的 了解血管内皮细胞调节血管紧张素转换酶 血管平滑肌反应性。尽管美国政府所扮演的角色 血管内皮细胞直到最近才被重视，现在它很容易 显然，这一细胞层是控制 血管张力。最近有人提出内皮细胞的偶联 为了使肌肉细胞平滑，可以在 这两种细胞类型。此外，最近的电生理数据支持 认为内皮细胞中至少有两种离子通道起作用的观点 控制血管活性物质释放的血流动力传感器 物质。因此，我们建议阐明其电生理特性。 更详细地描述内皮细胞的特性 外流和内流的差异及其形成机制(S) 调节；通过量化激动剂介导的钙内流 不同的途径来确定这些通量是否足以 解释观察到的钙瞬变；并确定是否不同- 从不同来源获得的内皮细胞在性质上存在差异 血管区域，以澄清由此产生的功能影响。 因此，我们建议针对以下具体目标：(1) 表征内皮细胞中不同的静息离子电流，(2) 将特定外向电流的存在与两个 诱发的钙瞬变和花生四烯酸的大小和时间进程 释放的酸，(3)表征电生理特性和 不同诱发内向和外向离子的调节基础 内皮细胞的电流，(4)确定诱发的基础 通过测量钙离子的大小和时间进程来实现钙瞬变 通过不同的途径进入细胞质，(5)确定是否 电生理特性和对不同激动剂的反应是 在从阻力血管中获得的内皮细胞中也是如此 微循环是指从大动脉获取的微循环。而眼前的 本应用程序的目标高度集中在对 血管内皮细胞的电生理特性及生化 结合血管活性介质的释放，我们不排除这种可能性 离子通道和离子传输系统在 内皮细胞生物学的调节。

The long term goal of the proposed research is to provide a better understanding of the mechanism by which the endothelium modulates the reactivity of vascular smooth muscle. Although the role played by the vascular endothelium was not appreciated until recently, it is now readily apparent that this cell layer is an essential element in the control of vascular tone. It has recently been proposed that coupling of endothelium to smooth muscle cells may provide for direct electrical signalling between these two cell types. In addition, recent electrophysiologic data support the view that at least two types of ion channels in the endothelium act as transducers of hemodynamic forces to control the release of vasoactive substances. Thus, we propose to elucidate the electrophysiologic properties of endothelial cells to: characterize in greater detail the properties of the different outward and inward currents and the mechanism(s) of their regulation; quantitate the agonist mediated calcium influx through different pathways to establish whether these fluxes are adequate to account for the calcium transient observed; and identify whether differ- ences in properties exist in endothelial cells obtained from different vascular regions, so as to clarify the resulting functional implications. We therefore propose to address the following specific aims: (1) to characterize the different resting ionic currents in endothelial cells, (2) to relate the presence of a particular outward current to both the magnitude and time course of the evoked calcium transient and arachidonic acid released, (3) to characterize the electrophysiologic properties and basis of regulation of the different evoked inward and outward ionic currents in endothelial cells, (4) to ascertain the basis of the evoked calcium transient by measuring the magnitude and time course of the Ca2+ flux through the different pathways into the cytoplasm, (5) to determine if the electrophysiologic properties and response to different agonists are the same in endothelial cells obtained from the resistance vessels and microcirculation as those obtained from large arteries. While the immediate goals of this application are highly focused on examination of the electrophysiologic properties of endothelial cells and the biochemical coupling to vasoactive mediator release, we do not exclude the possibility that ion channels and ion transport systems play a larger role in the regulation of the biology of endothelial cells.