Robarts Research Institute and the Department of Physiology & Pharmacology, University of Western Ontario, London, ON, Canada.
Robarts Research Institute and the Department of Physiology & Pharmacology, University of Western Ontario, London, ON, Canada.
Curr Top Membr. 2020;85:227-259. doi: 10.1016/bs.ctm.2020.01.006. Epub 2020 Feb 21.
Basal tone and perfusion control is set in cerebral arteries by the sensing of pressure and flow, key hemodynamic stimuli. These forces establish a contractile foundation within arterial networks upon which local neurovascular stimuli operate. This fundamental process is intimately tied to arterial V and the rise in cytosolic [Ca] by the graded opening of voltage-operated Ca channels. Arterial V is in turn controlled by a dynamic interaction among several resident ion channels, K being one of particular significance. As the name suggests, K displays strong inward rectification, retains a small outward component, potentiated by extracellular K and blocked by micromolar Ba. Cerebrovascular K is unique from other K currents as it is present in both smooth muscle and endothelium yet lacking in classical regulatory modulation. Such observations have fostered the view that K is nothing more than a background conductance, activated by extracellular K and which passively facilitates dilation. Recent work in cell model systems has; however, identified two membrane lipids, phosphatidylinositol 4,5-bisphosphate (PIP) and cholesterol, that interact with K2.x, to stabilize the channel in the preferred open or silent state, respectively. Translating this unique form of regulation, recent studies have demonstrated that specific lipid-protein interactions enable unique K populations to sense distinct hemodynamic stimuli and set basal tone. This review summarizes the current knowledge of vascular K channels and how the lipid and hemodynamic impact their activity.
基础张力和灌注控制由压力和流量的感知来设定，这是关键的血液动力学刺激因素。这些力量在动脉网络中建立了一个收缩基础，局部神经血管刺激在此基础上发挥作用。这个基本过程与动脉平滑肌细胞（V）以及通过电压门控钙通道的分级开放引起的细胞质[Ca]的升高密切相关。动脉 V 反过来又受到几种驻留离子通道之间的动态相互作用的控制，其中 K 通道是特别重要的一种。顾名思义，K 通道表现出强烈的内向整流，保留一个较小的外向成分，被细胞外 K 增强，并被微摩尔级别的 Ba 阻断。脑血管 K 不同于其他 K 电流，因为它存在于平滑肌和内皮细胞中，但缺乏经典的调节调节。这些观察结果促使人们认为 K 只不过是一种背景电导，由细胞外 K 激活，并被动促进扩张。然而，最近在细胞模型系统中的研究已经确定了两种膜脂质，磷脂酰肌醇 4,5-二磷酸（PIP）和胆固醇，它们分别与 K2.x 相互作用，分别将通道稳定在优先开放或沉默状态。这种独特的调节形式的转化，最近的研究表明，特定的脂质-蛋白相互作用使独特的 K 群体能够感知不同的血液动力学刺激并设定基础张力。本综述总结了血管 K 通道的最新知识，以及脂质和血液动力学如何影响它们的活性。
