CALCIUM CHANNELS AND CELLULAR CALCIUM HOMEOSTASIS IN SMOOTH MUSCLE

平滑肌中的钙通道和细胞钙稳态

• 批准号: 3736711
• 负责人: ANTONIO SCARPA
• 金额: --
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736711
• 关键词: atomic absorption spectrometry; calcium channel; cations; dihydropyridines; disease /disorder model; electron probe spectrometry; electrophysiology; fluorescent dye /probe; homeostasis; hypertension; magnesium; pharmacology; phosphorylation; spontaneous hypertensive rat; tissue /cell culture; vascular smooth muscle; vasopressins; voltage /patch clamp

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.

这个项目的总体目标是阐明主要和次要