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Kv7钾通道作为控制微血管张力的信号转导中间体。

Kv7 potassium channels as signal transduction intermediates in the control of microvascular tone.

作者信息

Byron Kenneth L, Brueggemann Lyubov I

机构信息

Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Maywood, IL, USA.

出版信息

Microcirculation. 2018 Jan;25(1). doi: 10.1111/micc.12419.

Abstract

Potassium channels are recognized as important regulators of cellular functions in most, if not all cell types. These cellular proteins assemble to form gated pores in the plasma membrane, which serve to regulate the flow of potassium ions (K ) from the cytosol to the extracellular space. In VSMCs, the open state of potassium channels enables the efflux of K and thereby establishes a negative resting voltage across the plasma membrane that inhibits the opening of VSCCs. Under these conditions, cytosolic Ca concentrations are relatively low and Ca -dependent contraction is inhibited. Recent research has identified Kv7 family potassium channels as important contributors to resting membrane voltage in VSMCs, with much of the research focusing on the effects of drugs that specifically activate or block these channels to produce corresponding effects on VSMC contraction and vascular tone. Increasingly, evidence is emerging that these channels are not just good drug targets-they are also essential intermediates in vascular signal transduction, mediating vasoconstrictor or vasodilator responses to a variety of physiological stimuli. This review will summarize recent research findings that support a crucial function of Kv7 channels in both positive (vasoconstrictive) and negative (vasorelaxant) regulation of microvascular tone.

摘要

钾通道被认为是大多数(即便不是所有)细胞类型中细胞功能的重要调节因子。这些细胞蛋白组装形成质膜上的门控孔道,用于调节钾离子(K⁺)从胞质溶胶流向细胞外空间。在血管平滑肌细胞(VSMCs)中,钾通道的开放状态使K⁺外流,从而在质膜上建立一个负的静息电压,抑制电压门控性钙通道(VSCCs)的开放。在这些条件下,胞质Ca²⁺浓度相对较低,Ca²⁺依赖性收缩受到抑制。最近的研究已确定Kv7家族钾通道是血管平滑肌细胞质膜静息电压的重要贡献者,大部分研究集中在特异性激活或阻断这些通道的药物对血管平滑肌细胞收缩和血管张力产生相应影响。越来越多的证据表明,这些通道不仅是良好的药物靶点——它们也是血管信号转导中的重要中间体,介导对各种生理刺激的血管收缩或血管舒张反应。本综述将总结最近的研究发现,这些发现支持Kv7通道在微血管张力的正向(血管收缩)和负向(血管舒张)调节中都发挥关键作用。

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