Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Vascular Biology and Vascular Medicine
Endophilin A2 Influences Volume-Regulated Chloride Current by Mediating ClC-3 Trafficking in Vascular Smooth Muscle Cells
Can-Zhao LiuXiang-Yu LiRen-Hong DuMin GaoMing-Ming MaFei-Ya LiEr-Wen HuangHong-Shuo SunGuan-Lei WangYong-Yuan Guan
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Supplementary material

2016 Volume 80 Issue 11 Pages 2397-2406


Background:Previous research has demonstrated that ClC-3 is responsible for volume-regulated Clcurrent (ICl.vol) in vascular smooth muscle cells (VSMCs). However, it is still not clear whether and how ClC-3 is transported to cell membranes, resulting in alteration ofICl.vol.

Methods and Results:Volume-regulated chloride current (ICl.vol) was recorded by whole-cell patch clamp recording, and Western blotting and co-immunoprecipitation were performed to examine protein expression and protein-protein interaction. Live cell imaging was used to observe ClC-3 transporting. The results showed that an overexpression of endophilin A2 could increaseICl.vol, while endophilin A2 knockdown decreasedICl.vol. In addition, the SH3 domain of endophilin A2 mediated its interaction with ClC-3 and promotes ClC-3 transportation from the cytoplasm to cell membranes. The regulation of ClC-3 channel activity was also verified in basilar arterial smooth muscle cells (BASMCs) isolated from endophilin A2 transgenic mice. Moreover, endophilin A2 increase VSMCs proliferation induced by endothelin-1 or hypo-osmolarity.

Conclusions:The present study identified endophilin A2 as a ClC-3 channel partner, which serves as a new ClC-3 trafficking insight in regulatingICl.volin VSMCs. This study provides a new mechanism by which endophilin A2 regulates ClC-3 channel activity, and sheds light on how ClC-3 is transported to cell membranes to play its critical role as a chloride channel in VSMCs function, which may be involved in cardiovascular diseases. (Circ J 2016; 80: 2397–2406)

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