ELECTROPHYIOLOGIC PROPERTIES OF ENDOTHELIAL CELLS

这项研究的长期目标是提供一个更好的 了解内皮细胞调节细胞增殖的机制， 血管平滑肌的反应性。虽然所发挥的作用， 血管内皮直到最近才被重视，现在很容易 很明显，这个细胞层是控制 血管张力最近有人提出， 平滑肌细胞之间的直接电信号 这两种细胞类型。此外，最近的电生理数据支持 内皮细胞中至少有两种类型的离子通道， 控制血管活性物质释放的血液动力学力传感器 物质.因此，我们建议阐明电生理特性 的内皮细胞：更详细地表征的性质， 不同的外向和内向电流及其机制 调节;定量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 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，我们建议达致下列具体目标：（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 诱发钙瞬变和花生四烯酸的幅度和时间过程 酸释放，（3）表征电生理特性， 调节不同诱发的内向和外向离子的基础 （4）确定诱发的基础; 通过测量Ca 2+的幅度和时间过程来测量钙瞬变 通过不同的途径进入细胞质，（5）以确定是否 电生理学特性和对不同激动剂的反应是 在从阻力血管获得的内皮细胞中也是如此， 从大动脉获得的微循环。虽然直接 本申请的目的是高度集中在检查 内皮细胞的电生理特性和生物化学特性 偶联到血管活性介质释放，我们不排除这种可能性， 离子通道和离子转运系统在 调节内皮细胞的生物学。

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.