Adenosine-activation of voltage-dependent K+ currents

电压依赖性 K 电流的腺苷激活

• 批准号: 6693853
• 负责人: CRISTINE L HEAPS
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-13 至 2004-11-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6693853
• 关键词: Adenosine; activation; voltage; dependent; K+

DESCRIPTION (provided by applicant): Potassium channel activation has been identified as an important component of adenosine-mediated relaxation in the coronary microcirculation. We have recently provided the first evidence for significant voltage-dependent (Kv) K+ channel contribution to ADO-mediated relaxation in porcine coronary arterioles. Our subsequent studies reveal that hypercholesterolemia abolishes the Kv channel contribution to ADO-mediated relaxation. Therefore, the primary objectives are to determine the Kv channel isoforms activated by ADO and the effect of hypercholesterolemia on these isoforms. Two specific aims will be addressed: Aim #1 will determine the Kv channel isoforms that contribute to ADO-activation of whole-cell K+ current in coronary arteriolar smooth muscle cells. Aim #2 will determine the expression of candidate Kv channel isoforms in coronary arteriolar smooth muscle from control and hypercholesterolemic animals. The overall hypothesis of this research proposal is that hypercholesterolemia alters the Kv channel isoforms present in the coronary microcirculation such that those that contribute to ADO-mediated relaxation are no longer expressed.

描述(由申请人提供)：钾通道激活已被确认为冠脉微循环中腺苷介导的松弛的重要组成部分。我们最近首次提出了电压依赖性(Kv)钾通道在猪冠状动脉小动脉ADO介导的松弛中的重要作用的证据。我们随后的研究表明，高胆固醇血症取消了Kv通道对ADO介导的松弛的贡献。因此，我们的主要目标是确定ADO激活的Kv通道亚型以及高胆固醇血症对这些亚型的影响。两个具体的目标将被解决：目标#1将确定有助于激活冠状小动脉平滑肌细胞全细胞钾电流的Kv通道亚型。目的#2将测定来自对照组和高胆固醇血症动物的冠状小动脉平滑肌中候选Kv通道亚型的表达。这项研究的总体假设是，高胆固醇血症改变了冠脉微循环中存在的Kv通道亚型，使那些有助于ADO介导的松弛的亚型不再表达。