ELECTROMECHANICAL COUPLING IN CORONARY ARTERY

描述：本申请提出了一种研究， 冠状血管舒张的机制。 血管舒张通常是 与平滑肌细胞质Ca 2+水平的降低有关。 因此，了解导致 电压依赖性Ca 2+通道的关闭， 减少Ca 2+进入细胞。总体假设 电压依赖性Ca 2+通道是目前研究的一个重要方面。 直接由血管扩张剂以及间接通过 伴随K+开放的膜电位变化 渠道此外，建议这些问题的具体性质 血管扩张剂之间的效果显著不同。 到 调查这一假设实验提出使用 膜片钳技术在分离的平滑肌细胞上表征 血管舒张剂对K+通道和电压依赖性的作用 Ca 2+通道要将这些通道效应与 完整组织中的血管扩张剂、膜电位和 离体冠状动脉环段舒张（+/-内皮） 将被衡量。血管扩张的途径， 在本申请中研究包括：1）腺苷和cAMP，2） 内皮源性超极化因子 “EDHF”，4）ATP和5）K+通道开放剂lemakalim。整体 这项工作的目的是了解这些生理上的 相关的血管扩张剂调节K+和Ca 2+通道活性， 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.