ELECTROMECHANICAL COUPLING IN CORONARY ARTERY

描述：此应用程序建议对 冠状动脉血管扩张的机制。血管扩张通常是 与平滑肌细胞内钙离子水平下降有关。 因此，重要的是要了解导致 电压依赖性钙通道的关闭，从而导致 减少细胞内钙离子的进入。总体假设 目前的研究表明，电压依赖的钙通道是 由血管扩张剂直接调节，也通过血管扩张剂间接调节 钾离子开放过程中膜电位的变化 频道。此外，还建议将这些问题的具体性质 不同的血管扩张剂的效果有很大不同。至 为了研究这一假设，提出了使用 膜片钳技术对分离的平滑肌细胞特性的研究 血管扩张剂对K+通道和电压依赖性的作用 钙离子通道。要将这些通道效果与以下操作相关联 完整组织中的血管扩张剂，膜电位和 冠状动脉离体环节段(+/-内皮)的松弛 将会被测量。血管扩张剂途径将是 本申请的研究内容包括：1)腺苷和cAMP，2) 一氧化氮与cGMP，3)内皮源性超极化因子 “EDHF”，4)ATP和5)K+通道开放剂Lemakalim。整体而言 这项工作的目标是了解这些生理上是如何 相关血管扩张剂调节K+和Ca~(2+)通道活性，从而 更好地了解冠状动脉张力是如何调节的。

DESCRIPTION: This application proposes an investigation of the mechanisms of coronary vasodilation. Vasodilation is generally associated with a decrease in smooth muscle cytoplasmic Ca2+ levels. Therefore, it is critical to understand the mechanisms which lead to the closing of voltage dependent Ca2+ channels and consequently a reduction in the entry of Ca2+ into the cell. The overall hypothesis for the present studies is that voltage dependent Ca2+ channels are modulated both directly by vasodilators as well as indirectly via the changes in membrane potential which accompany the opening of K+ channels. Further, it is proposed that the specific nature of these effects differs significantly between vasodilators. To investigate this hypothesis experiments are proposed using the patch clamp technique on isolated smooth muscle cells to characterize the actions of vasodilators on both K+ channels and voltage dependent Ca2+ channels. To relate these channel effects to the actions of vasodilators in the intact tissue, membrane potential and relaxation of isolated ring segments of coronary artery (+/- endothelium) will be measured. The vasodilator pathways which will be investigated in this application include: 1) adenosine and cAMP, 2) nitric oxide and cGMP, 3) endothelium derived hyperpolarizing factor "EDHF", 4) ATP and 5) the K+ channel opener lemakalim. The overall objective of this work is to understand how these physiologically relevant vasodilators modulate K+ and Ca2+ channel activity and thus better understand how coronary arterial tone is regulated.