Adenosine-activation of voltage-dependent K+ currents

描述（由申请方提供）：钾通道激活已被确定为腺苷介导的冠状动脉微循环舒张的重要组成部分。我们最近提供了第一个证据，证明在猪冠状小动脉中，电压依赖性（Kv）K+通道对ADO介导的舒张有重要作用。我们随后的研究表明，高胆固醇血症废除了Kv通道的贡献，ADO介导的放松。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。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ADO激活的Kv通道亚型。 目的#2将确定来自对照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，高胆固醇血症改变了冠状动脉微循环中存在的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。

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.