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增强信号:内皮内向整流钾通道

Boosting the signal: Endothelial inward rectifier K channels.

作者信息

Jackson William F

机构信息

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.

出版信息

Microcirculation. 2017 Apr;24(3). doi: 10.1111/micc.12319.

Abstract

Endothelial cells express a diverse array of ion channels including members of the strong inward rectifier family composed of K 2 subunits. These two-membrane spanning domain channels are modulated by their lipid environment, and exist in macromolecular signaling complexes with receptors, protein kinases and other ion channels. Inward rectifier K channel (K ) currents display a region of negative slope conductance at membrane potentials positive to the K equilibrium potential that allows outward current through the channels to be activated by membrane hyperpolarization, permitting K to amplify hyperpolarization induced by other K channels and ion transporters. Increases in extracellular K concentration activate K allowing them to sense extracellular K concentration and transduce this change into membrane hyperpolarization. These properties position K to participate in the mechanism of action of hyperpolarizing vasodilators and contribute to cell-cell conduction of hyperpolarization along the wall of microvessels. The expression of K in capillaries in electrically active tissues may allow K to sense extracellular K , contributing to functional hyperemia. Understanding the regulation of expression and function of microvascular endothelial K will improve our understanding of the control of blood flow in the microcirculation in health and disease and may provide new targets for the development of therapeutics in the future.

摘要

内皮细胞表达多种离子通道,包括由K2亚基组成的强内向整流家族成员。这些跨膜两结构域通道受其脂质环境调节,并存在于与受体、蛋白激酶和其他离子通道形成的大分子信号复合物中。内向整流钾通道(K)电流在膜电位高于钾平衡电位时显示出负斜率电导区域,这使得通道的外向电流可被膜超极化激活,从而使钾离子放大由其他钾通道和离子转运体诱导的超极化。细胞外钾浓度的升高会激活钾通道,使其能够感知细胞外钾浓度并将这种变化转化为膜超极化。这些特性使钾通道参与超极化血管舒张剂的作用机制,并有助于超极化在微血管壁上的细胞间传导。电活动组织中毛细血管钾通道的表达可能使钾通道感知细胞外钾,从而促进功能性充血。了解微血管内皮钾通道表达和功能的调节将增进我们对健康和疾病状态下微循环血流控制的理解,并可能为未来治疗药物的开发提供新靶点。

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