Volume activated chloride channels (also termed VSOAC, volume-sensitive organic osmolyte/anion channel; VRC, volume regulated channel and VSOR, volume expansion-sensing outwardly rectifying anion channel) participate in regulatory volume decrease (RVD) in response to cell swelling. VRAC may also be important for several other processes including the regulation of membrane excitability, transcellular Cl^- transport, angiogenesis, cell proliferation, necrosis, apoptosis, glutamate release from astrocytes, insulin (INS, P01308) release from pancreatic β cells and resistance to the anti-cancer drug, cisplatin (reviewed by [1-4]). VRAC may not be a single entity, but may instead represent a number of different channels that are expressed to a variable extent in different tissues and are differentially activated by cell swelling. In addition to ClC-3 expression products (see above) several former VRAC candidates including MDR1 (ABCB1 P-glycoprotein), Icln, Band 3 anion exchanger and phospholemman are also no longer considered likely to fulfil this function (see reviews [3,5]).

In addition to conducting monovalent anions, in many cell types the activation of VRAC by a hypotonic stimulus can allow the efflux of organic osmolytes such as amino acids and polyols that may contribute to RVD.

1. Best L, Brown PD, Sener A, Malaisse WJ. (2010) Electrical activity in pancreatic islet cells: The VRAC hypothesis. Islets, 2 (2): 59-64. [PMID:21099297]

2. Mulligan SJ, MacVicar BA. (2006) VRACs CARVe a path for novel mechanisms of communication in the CNS. Sci STKE, 2006 (357): pe42. [PMID:17047222]

3. Nilius B, Droogmans G. (2003) Amazing chloride channels: an overview. Acta Physiol Scand, 177 (2): 119-47. [PMID:12558550]

4. Okada Y, Sato K, Numata T. (2009) Pathophysiology and puzzles of the volume-sensitive outwardly rectifying anion channel. J Physiol (Lond.), 587 (Pt 10): 2141-9. [PMID:19171657]

5. Sardini A, Amey JS, Weylandt KH, Nobles M, Valverde MA, Higgins CF. (2003) Cell volume regulation and swelling-activated chloride channels. Biochim Biophys Acta, 1618 (2): 153-62. [PMID:14729152]