CALCIUM CHANNELS AND CELLULAR CALCIUM HOMEOSTASIS IN SMOOTH MUSCLE

这个项目的总体目标是阐明主要的和次要的 缺陷性血管内皮细胞钙、钠离子升高 高血压动物细胞(VSM)。这项调查将需要 趋同于三大资产的重要问题的优势： A)将在其中放置高血压大鼠动物模型的设施(核心b) 有严格记录的维持和高血压状况；b)多个 方法(原子吸光度、荧光指示剂和电子探针 微量分析)，以测量高血压VSM细胞的钙和钠离子的增加， 不同细胞间的分布和细胞内的再分布 这些阳离子；c)现代膜片钳电生理方法。 提出的研究的一个主要重点是在VSM细胞中使用，其中Na 和钙的增加，膜片钳技术研究的可能性 L、T型和B型的数量、门控和调节的变化 (一种在静息膜上零星开放的新型钙通道 潜力)。 工作假说是，在高血压VSM细胞中，有一种 钙通道数量或调节的原发或继发性变化(S) 这会导致这些细胞内钙离子和钠离子的增加。这样的发现 不仅可以阐明高血压的原因或后果，而且 将对药理干预具有重要的内涵。在……里面 此外，它将为现有的微薄的知识增加重要的知识 细胞内这三种钙通道的调控信息 正常的平滑肌细胞。最后，它将提供以下方面的定量数据 正常人细胞内钙、钠、镁离子含量及其分布 和高血压的平滑肌细胞。

The overall objective of this project is to elucidate primary and secondary defects leading to an increase of Ca2+ and Na+ in vascular smooth muscle cells (VSM) of hypertensive animals. This investigation will take advantage of the convergency to an important problem of three major assets: a) a facility (Core b) where hypertensive rat animal models will be maintained and hypertensive conditions rigorously documented; b) a multi approach (atomic absorbance, fluorescence indicators and electro probe microanalysis) to measure hypertensive VSM cells Ca2+ and Na+ increase, the distribution among various cells and the intracellular redistribution of these cations; c) a modern patch clamp electrophysiological approach. A major emphasis of the research proposed is to use in VSM cells, where Na and Ca are increased, patch clamp techniques to investigate possible alterations in number, gating and regulation of L-type, T-type and B-type (a novel calcium channel which sporadically opens at resting membrane potential). The working hypothesis is that in hypertensive VSM cells, there is a primary or secondary change in number or in the regulation of Ca channel(s) which leads to an increase in Ca2+ and Na+ in these cells. Such a finding could not only shed light on causes or consequences of hypertension, but will have important connotations for pharmacological intervention. In addition, it will add significant knowledge to the meager existing information on the regulation of these three types of Ca2+ channels in normal smooth muscle cells. Finally, it will provide quantitative data on Ca2+, Na+ and Mg2+ content and their intracellular distribution in normal and hypertensive smooth muscle cells.