CALCIUM CHANNELS AND CELLULAR CALCIUM HOMEOSTASIS IN SMOOTH MUSCLE

本项目的总体目标是阐明小学和中学 导致血管平滑肌中Ca 2+和Na+增加的缺陷 细胞（VSM）的高血压动物。 这次调查将 优势的收敛到一个重要的问题，三大资产： a）设施（核心B），其中高血压大鼠动物模型将被 严格记录的维持和高血压状况; B）多种 方法（原子吸收、荧光指示剂和电子探针 微量分析）测定高血压大鼠VSM细胞Ca 2+和Na+的增加， 在各种细胞之间的分布和细胞内的再分布 这些阳离子; c）现代膜片钳电生理学方法。 该研究的一个主要重点是在VSM细胞中使用，其中Na 和钙增加，膜片钳技术，以调查可能的 L型、T型和B型的数量、门控和调节的改变 （一种新的钙通道，在静息膜上偶尔打开 潜力）。 工作假设是，在高血压VSM细胞中， Ca通道数量或调节的原发性或继发性变化 这导致这些细胞中Ca 2+和Na+的增加。 这样的发现 不仅可以揭示高血压的原因或后果， 将对药物干预具有重要意义。 在 此外，它将增加显着的知识，以微薄的现有 关于这三种类型的Ca 2+通道的调节的信息， 正常平滑肌细胞 最后，它将提供关于以下方面的定量数据： 正常人心肌细胞内Ca ~（2+）、Na ~+、Mg ~（2+）含量及其细胞内分布 和高血压平滑肌细胞。

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.