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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

Received: 2018-06-14　　Accepted: 2018-11-11

Corresponding author: 刘慧荣　　E-mail: liuhr2000@ccmu.edu.cn

DOI: 10.13294/j.aps.2019.0013

Citing This Article：

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