CA2+ SIGNALING IN ARTERIAL SMOOTH MUSCLE CELLS

动脉平滑肌细胞中的 CA2 信号传导

• 批准号: 6536738
• 负责人: SEAN M WILSON
• 金额: $ 4.62万
• 依托单位: UNIVERSITY OF NEVADA RENO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6536738
• 关键词: acidity /alkalinity; calcium flux; calcium ion; confocal scanning microscopy; dogs; electrophysiology; fluorescence microscopy; hypoxia; ion transport; membrane potentials; mitochondria; oxygen tension; postdoctoral investigator; pulmonary artery; renal artery; sarcoplasmic reticulum; vascular smooth muscle; vasomotion

The overall goal of this project is to gain a more complete understanding of Ca2+ homeostasis and signaling processes in arterial smooth muscle cells and to study the mechanism underlying hypoxic induced pulmonary vasoconstriction. The high-resistance arteries of the pulmonary arteries constrict shunting blood to well-oxygenated areas of the lung while renal arteries relax increasing flow, as do most vascular beds. By studying smooth muscle cells from pulmonary and renal arteries, mechanisms specific to the pulmonary vasculature can be discriminated from those that are more general. Specifically, three hypotheses will be tested: 1) That Ca2+ homeostasis in pulmonary arterial smooth muscle cells (PASMC) is governed by interactions between sarcoplasmic reticulum (SR), mitochondria, and extracellular Ca2+ sources; 2) That Sr Ca2+ release alters the membrane potential and that hypoxia modulates this process in PASMC; and 3) That intracellular pH changes affect Ca+ signaling and that hypoxia alters intracellular pH in PASMC. These hypotheses will be tested in freshly isolated canine pulmonary and renal arterial smooth muscle cells using whole-cell and laser-confocal fluorescence microscopy in combination with cell electrophysiology techniques. This study will help fill an existing gap in knowledge regarding the role of Ca2+ signaling processes in vascular reactivity of the pulmonary circulation. The medical significance is that the results obtained may reveal important cellular mechanisms responsible for pulmonary and systemic hypertension and could lead to the development of new drugs and therapeutic strategies to treat or prevent these conditions.

该项目的总体目标是更全面地了解动脉平滑肌细胞中的 Ca2+ 稳态和信号传导过程，并研究缺氧诱导肺血管收缩的机制。肺动脉的高阻力动脉会收缩将血液分流至肺部氧合良好的区域，而肾动脉则放松，增加流量，就像大多数血管床一样。通过研究肺动脉和肾动脉的平滑肌细胞，可以将肺脉管系统特有的机制与更一般的机制区分开来。具体来说，将测试三个假设：1）肺动脉平滑肌细胞（PASMC）中的Ca2+稳态由肌浆网（SR）、线粒体和细胞外Ca2+来源之间的相互作用控制； 2) Sr Ca2+ 的释放改变了 PASMC 的膜电位，缺氧调节了这一过程； 3) 细胞内 pH 值的变化影响 Ca+ 信号传导，缺氧会改变 PASMC 的细胞内 pH 值。这些假设将使用全细胞和激光共聚焦荧光显微镜结合细胞电生理学技术在新鲜分离的犬肺动脉和肾动脉平滑肌细胞中进行测试。这项研究将有助于填补关于 Ca2+ 信号传导过程在肺循环血管反应性中的作用的现有知识空白。医学意义在于，所获得的结果可能揭示导致肺动脉高压和全身性高血压的重要细胞机制，并可能导致开发治疗或预防这些疾病的新药和治疗策略。

项目成果

Comparative capacitative calcium entry mechanisms in canine pulmonary and renal arterial smooth muscle cells.

犬肺动脉和肾动脉平滑肌细胞的比较电容性钙进入机制。

• 发表时间: 2002-09-15
• 作者: Wilson, Sean M;Mason, Helen S;Smith, Gregory D;Nicholson, Neil;Johnston, Louise;Janiak, Robert;Hume, Joseph R
• 通讯作者: Hume, Joseph R