Adenosine-activation of voltage-dependent K+ currents

电压依赖性 K 电流的腺苷激活

• 批准号: 6584215
• 负责人: CRISTINE L HEAPS
• 金额: $ 4.81万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-11 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6584215
• 关键词: adenosine; arterioles; cardiac myocytes; electrophysiology; heart circulation; hypercholesterolemia; ion channel blocker; membrane activity; microcirculation; muscle relaxation; polymerase chain reaction; postdoctoral investigator; potassium channel; protein isoforms; smooth muscle; swine; voltage /patch clamp; voltage gated channel; western blottings

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）：钾通道激活已被确定为冠状动脉微循环中腺苷介导的舒张的重要组成部分。我们最近首次提供了电压依赖性（Kv） K+通道对ado介导的猪冠状动脉舒张的显著贡献的证据。我们随后的研究表明，高胆固醇血症消除了Kv通道对ado介导的松弛的贡献。因此，主要目的是确定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。两个具体目标将被解决：目标1将确定有助于ado激活冠状动脉平滑肌细胞全细胞K+电流的Kv通道异构体。目的2将确定候选Kv通道异构体在对照和高胆固醇血症动物冠状动脉平滑肌中的表达。本研究建议的总体假设是，高胆固醇血症改变了存在于冠状动脉微循环中的Kv通道亚型，使得那些有助于ado介导的舒张的亚型不再表达。