微血管中的KIR通道:调节特性和脂质血流动力学环境。

4区 生物学 Q4 Biochemistry, Genetics and Molecular Biology
Current topics in membranes Pub Date : 2020-01-01 Epub Date: 2020-02-21 DOI:10.1016/bs.ctm.2020.01.006
Maria Sancho, Donald G Welsh
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引用次数: 3

摘要

脑动脉的基底张力和灌注控制是通过对压力和流量的感知来设定的,这是关键的血流动力学刺激。这些力量在动脉网络中建立了收缩基础,局部神经血管刺激在此基础上起作用。这一基本过程与动脉VM密切相关,并通过电压操作的Ca2+通道逐步开放细胞质[Ca2+]。动脉VM反过来由几个常驻离子通道之间的动态相互作用控制,KIR是其中特别重要的一个。顾名思义,KIR表现出强烈的向内整流,保留了少量的向外成分,由细胞外K+增强,并被微摩尔Ba2+阻断。脑血管KIR与其他K+电流不同,它既存在于平滑肌中,也存在于内皮中,但缺乏经典的调节。这样的观察结果促进了这样的观点,即KIR只不过是一种背景电导,由细胞外K+激活,被动地促进扩张。最近对细胞模型系统的研究;然而,发现了两种膜脂,磷脂酰肌醇4,5-二磷酸(PIP2)和胆固醇,与KIR2相互作用。X,分别将通道稳定在首选的打开或沉默状态。翻译这种独特的调节形式,最近的研究表明,特定的脂质-蛋白质相互作用使独特的KIR群体能够感知不同的血流动力学刺激并设定基础基调。本文综述了血管KIR通道的现状,以及血脂和血流动力学对其活性的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
KIR channels in the microvasculature: Regulatory properties and the lipid-hemodynamic environment.

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 VM and the rise in cytosolic [Ca2+] by the graded opening of voltage-operated Ca2+ channels. Arterial VM is in turn controlled by a dynamic interaction among several resident ion channels, KIR being one of particular significance. As the name suggests, KIR displays strong inward rectification, retains a small outward component, potentiated by extracellular K+ and blocked by micromolar Ba2+. Cerebrovascular KIR 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 KIR 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 (PIP2) and cholesterol, that interact with KIR2.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 KIR populations to sense distinct hemodynamic stimuli and set basal tone. This review summarizes the current knowledge of vascular KIR channels and how the lipid and hemodynamic impact their activity.

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来源期刊
Current topics in membranes
Current topics in membranes 生物-生化与分子生物学
CiteScore
3.50
自引率
0.00%
发文量
10
审稿时长
>12 weeks
期刊介绍: Current Topics in Membranes provides a systematic, comprehensive, and rigorous approach to specific topics relevant to the study of cellular membranes. Each volume is a guest edited compendium of membrane biology.
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