血管紧张素II对血管平滑肌细胞中大电导钙激活钾通道的多重调节作用
尹晓辰¹, 张苏丽^1,2, 刘慧荣^1,2,3,*
1首都医科大学基础医学院生理学与病理生理学系，北京 100069；²首都医科大学代谢紊乱相关心血管疾病北京市重点实验室，北京 100069；³首都医科大学代谢紊乱相关心血管疾病国际合作实验室，北京 100069
摘要
肾素-血管紧张素系统(renin-angiotensin system, RAS)是影响血管平滑肌细胞张力的重要因素。RAS主要活性物质血管紧张素II (angiotensin II, Ang II)可通过激活血管紧张素II-1型受体(angiotensin II type 1 receptor, AT1R)升高胞内Ca2+浓度，收缩平滑肌细胞。大电导钙激活钾(large-conductance Ca2+- and voltage-activated potassium, BK)通道是血管平滑肌细胞中分布最广、表达最多的钾离子通道，在维持细胞膜电位和胞内钾钙平衡中发挥重要作用。血管平滑肌细胞上的BK通道主要包含α与β1两种亚基。其中功能亚基BKα上分布有膜电位及Ca2+感受器。因此当膜电位或细胞内Ca2+浓度升高时会反馈性引起BK通道开放。然而，越来越多的研究显示，尽管Ang II可升高胞内Ca2+浓度，但却通过激活PKC通路、促进AT1R与BKα通道形成的异源二聚体内吞、加快α与β1亚基解离等途径抑制BK通道的表达和功能。在一些情况下，Ang II对BK通道也可表现出激活作用，但机制尚不完全明确。该综述总结了Ang II对BK通道抑制或激活两方面效应的可能原因，为改善细胞内离子失衡提供理论依据。
关键词： 大电导钙激活钾通道; 血管紧张素II; 血管紧张素II-1型受体; 血管平滑肌
分类号：R331.3+2

Multiple regulatory effects of angiotensin II on the large-conductance Ca2+- and voltage-activated potassium channel in vascular smooth muscle cells
YIN Xiao-Chen¹, ZHANG Su-Li^1,2, LIU Hui-Rong^1,2,3,*
1Department of Physiology and Pathophysiology, School of Basic Medicine, Capital Medical University, Beijing 100069, China；²Beijing Key Laboratory of Cardiovascular Diseases and Related Metabolic Dysfunction, Capital Medical University, Beijing 100069, China；³International Cooperative Laboratory of Cardiovascular Diseases and Related Metabolic Dysfunction, Capital Medical University, Beijing 100069, China
Abstract
Renin-angiotensin system (RAS) is involved in the regulation of vascular smooth muscle cell (VSMC) tension. Angiotensin II (Ang II) as the main effector molecule of RAS can increase the intracellular Ca2+ concentration and cause VSMCs contraction by activating angiotensin II type 1 receptor (AT1R). The large-conductance Ca2+- and voltage-activated potassium (BK) channel is an essential potassium channel in VSMCs, playing an important role in maintaining membrane potential and intracellular potassium-calcium balance. The BK channel in VSMCs mainly consists of α and β1 subunits. Functional BKα subunits contain voltage-sensors and Ca2+ binding sites. Hence, increase in the membrane potential or intracellular Ca2+ concentration can trigger the opening of the BK channel by mediating transient K+ outward current in a negative regulatory manner. However, increasing evidence has shown that although Ang II can raise the intracellular Ca2+ concentration, it also inhibits the expression and function of the BK channel by activating the PKC pathway, internalizing AT1R-BKα heterodimer, or dissociating α and β1 subunits. Under some specific conditions, Ang II can also activate the BK channel, but the underlying mechanism remains unknown. In this review, we summarize the potential mechanisms underlying the inhibitory or activating effect of Ang II on the BK channel, hoping that it could provide a theoretical basis for
improving intracellular ion imbalance.


Key words: large-conductance Ca2+- and voltage-activated potassium channel; angiotensin II; angiotensin II type 1 receptor; vascular smooth muscle

收稿日期：2018-06-14　　录用日期：2018-11-11
通讯作者：刘慧荣　　E-mail: liuhr2000@ccmu.edu.cn
DOI: 10.13294/j.aps.2019.0013
引用本文：
尹晓辰, 张苏丽, 刘慧荣. 血管紧张素II对血管平滑肌细胞中大电导钙激活钾通道的多重调节作用[J]. 生理学报 2019; 71 (2): 187-195.
YIN Xiao-Chen, ZHANG Su-Li, LIU Hui-Rong. Multiple regulatory effects of angiotensin II on the large-conductance Ca2+- and voltage-activated potassium channel in vascular smooth muscle cells. Acta Physiol Sin 2019; 71 (2): 187-195



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