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）：钾通道激活已被确定为冠状微循环中腺苷介导的舒张的重要组成部分。我们最近提供了第一个证据，证明电压依赖性 (Kv) K+ 通道对 ADO 介导的猪冠状动脉舒张有显着贡献。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。将解决两个具体目标：目标 #1 将确定有助于冠状动脉平滑肌细胞中全细胞 K+ 电流的 ADO 激活的 Kv 通道亚型。 目标#2 将确定对照动物和高胆固醇血症动物的冠状动脉平滑肌中候选 Kv 通道亚型的表达。本研究提案的总体假设是，高胆固醇血症会改变冠状动脉微循环中存在的 Kv 通道亚型，从而导致那些有助于 ADO 介导的舒张的亚型不再表达。