KCa channels and conducted vasodilation

描述（由申请人提供）：血管舒张的传导反映了超极化电流通过间隙连接通道沿血管壁的传播，并用于协调串联和平行的阻力血管段的反应。钙活化钾通道（KCa）启动超极化反应，但其在启动传导超极化和血管舒张中的功能作用尚不清楚。使用分离的加压仓鼠牵开器喂养动脉，我的中心目的是研究KCa在传导超极化和血管舒张的启动中的功能。与从大脑中分离出来的阻力微血管不同，这些供血动脉很长（3-4毫米）且无分支，因此非常适合研究传导血管舒张的机制。利用选择性KCa阻滞剂的应用，结合直径和电生理测量，我将回答：1)哪种KCa是启动传导超极化和血管舒张所必需的，以及2)毒蕈碱受体和KCa激活之间的功能偶联，这些KCa激活位于内皮细胞各自的腔内和腔内区域。糖尿病、高血压、动脉粥样硬化和中风的一个关键因素是内皮功能障碍与抗血管收缩能力受损相关。了解特定离子通道的作用和解决内皮细胞介导的血管舒张的极性将提供新的见解，可能会加强与血管疾病相关的病理的预防和治疗。

DESCRIPTION (provided by applicant): The conduction of vasodilation reflects the spread of hyperpolarizing current along the vessel wall through gap junction channels, and serves to coordinate responses in serial and parallel segments of the resistance vasculature. The calcium-activated potassium channels (KCa) initiate hyperpolarizing responses, but their functional role in the initiation of conducted hyperpolarization and vasodilation is unclear. Using isolated, pressurized hamster retractor feed arteries my central aim is to investigate the function of the KCa in the initiation of conducted hyperpolarization and vasodilation. Unlike resistance microvessels isolated from the brain, these feed arteries are long (3-4 mm) and unbranched, and therefore ideal for studying the mechanisms of conducted vasodilation. Utilizing selective KCa blocker application in conjunction with diameter and electrophysiological measurements I will answer: 1) which KCa are necessary for the initiation of a conducted hyperpolarization and vasodilation, and 2) is the functional coupling between muscarinic receptor and KCa activation localized within respective abluminal and luminal domains of endothelial cells. A key factor in diabetes, hypertension, atherosclerosis, and stroke is endothelial dysfunction associated with the impaired ability to oppose vasoconstriction. Understanding the role of specific ion channels and resolving the polarity of endothelial cell-mediated vasodilation will provide new insight that may enhance the prevention and treatment of pathologies associated with vascular disease.