Pedersen Stine F, Okada Yasunobu, Nilius Bernd
Section for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark.
SOKENDAI (The Graduate University for Advanced Studies), Kanagawa, 240-0193, Japan.
Pflugers Arch. 2016 Mar;468(3):371-83. doi: 10.1007/s00424-015-1781-6. Epub 2016 Jan 6.
The volume-regulated anion channel (VRAC), also known as the volume-sensitive outwardly rectifying (VSOR) anion channel or the volume-sensitive organic osmolyte/anion channel (VSOAC), is essential for cell volume regulation after swelling in most vertebrate cell types studied to date. In addition to its role in cell volume homeostasis, VRAC has been implicated in numerous other physiological and pathophysiological processes, including cancer, ischemic brain edema, cell motility, proliferation, angiogenesis, programmed cell death, and excitotoxic glutamate release. Although VRAC has been extensively biophysically, pharmacologically, and functionally characterized, its molecular identity was highly controversial until the recent identification of the leucine-rich repeats containing 8A (LRRC8A) protein as essential for the VRAC current in multiple cell types and a likely pore-forming subunit of VRAC. Members of this distantly pannexin-1-related protein family form heteromers, and in addition to LRRC8A, at least another LRRC8 family member is required for the formation of a functional VRAC. This review summarizes the biophysical and pharmacological properties of VRAC, highlights its main physiological functions and pathophysiological implications, and outlines the search for its molecular identity.
容积调节性阴离子通道（VRAC），也被称为容积敏感性外向整流（VSOR）阴离子通道或容积敏感性有机渗透物/阴离子通道（VSOAC），对于迄今为止研究的大多数脊椎动物细胞类型在肿胀后的细胞容积调节至关重要。除了在细胞容积稳态中的作用外，VRAC还与许多其他生理和病理生理过程有关，包括癌症、缺血性脑水肿、细胞运动、增殖、血管生成、程序性细胞死亡和兴奋性毒性谷氨酸释放。尽管VRAC已经在生物物理学、药理学和功能方面得到了广泛的表征，但其分子身份一直存在很大争议，直到最近富含亮氨酸重复序列8A（LRRC8A）蛋白被确定为多种细胞类型中VRAC电流所必需的，并且可能是VRAC的孔形成亚基。这个与泛连接蛋白1关系较远的蛋白质家族成员形成异源寡聚体，并且除了LRRC8A之外，至少还需要另一个LRRC8家族成员才能形成功能性的VRAC。这篇综述总结了VRAC的生物物理和药理学特性，强调了其主要的生理功能和病理生理意义，并概述了对其分子身份的探索。
