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沿着血管壁通过间隙连接通道的扩散，并用于协调阻力血管系统的串联和并联节段中的反应。钙激活钾通道（KCa）启动超极化反应，但其在启动传导性超极化和血管舒张中的功能作用尚不清楚。使用隔离，加压仓鼠牵开器饲料动脉，我的主要目的是调查的KCa在启动传导超极化和血管舒张的功能。与从脑中分离的阻力微血管不同，这些供血动脉长（3-4 mm）且无分支，因此是研究传导性血管舒张机制的理想选择。利用选择性KCa阻滞剂应用结合直径和电生理测量，我将回答：1）哪些KCa是启动传导性超极化和血管舒张所必需的，以及2）是位于内皮细胞的相应近腔和腔域内的毒蕈碱受体和KCa激活之间的功能性偶联。糖尿病、高血压、动脉粥样硬化和中风的关键因素是与抵抗血管收缩的能力受损相关的内皮功能障碍。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.