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Ca^(2+)浓度,收缩平滑肌细胞。大电导钙激活钾(large-conductance Ca^(2+)-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Ca^(2+)感受器。因此当膜电位或细胞内Ca^(2+)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Ca^(2+)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。
Renin-angiotensin system(RAS)is involved in the regulation of vascular smooth muscle cell(VSMC)tension.AngiotensinⅡ(AngⅡ)as the main effector molecule of RAS can increase the intracellular Ca2+concentration and cause VSMCs contraction by activating angiotensinⅡtype 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 ofαandβ1 subunits.Functional BKαsubunits 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 AngⅡcan raise the intracellular Ca2+concentration,it also inhibits the expression and function of the BK channel by activating the PKC pathway,internalizing AT1R-BKαheterodimer,or dissociatingαandβ1 subunits.Under some specific conditions,AngⅡcan 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 AngⅡon the BK channel,hoping that it could provide a theoretical basis for improving intracellular ion imbalance.
作者
尹晓辰
张苏丽
刘慧荣
YIN Xiao-Chen;ZHANG Su-Li;LIU Hui-Rong(Department of Physiology and Pathophysiology,School of Basic Medicine;Beijing Key Laboratory of Cardiovascular Diseases and Related Metabolic Dysfunction;International Cooperative Laboratory of Cardiovascular Diseases and Related Metabolic Dysfunction,Capital Medical University,Beijing 100069,China)
出处
《生理学报》
CAS
CSCD
北大核心
2019年第2期187-195,共9页
Acta Physiologica Sinica
基金
supported by grants from the Major Program of the National Natural Science Foundation of China (No. 91539205)
the National Natural Science Foundation of China (No. 31771267)
Beijing Natural Science Foundation Program
Scientific Research Key Program of Beijing Municipal Commission of Education (No. KZ201810025039)
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
large-conductance Ca2+-and voltage-activated potassium channel
angiotensinⅡ
angiotensinⅡtype 1 receptor
vascular smooth muscle
