Volume-Regulated Anion Channels and the Control of a Simple Cell Behavior

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Abstract
Volume-regulated anion channels (VRAC) are ubiquitous ion channels that are normally nonconducting, but can be opened upon cell swelling. Described initially in T lymphocytes, VRAC are characterized by activation in response to a hypotonic challenge, outward rectification of the current-voltage relationship, and a selectivity of I– > NO–3 > Br- > C1- > propionate > gluconate. Currents carried by these channels play a role in the mechanism of cell volume regulation such that the outward flow of Cl– results in the subsequent depolarization and activation of K+ channels resulting in water efflux which ultimately allows the cell to recover its volume following exposure to a hypotonic challenge. VRAC may also play a role in lymphocyte activation and proliferation. The regulation of these currents is not fully understood, but ATP is required for maintenance of the current and cytoskeletal integrity is likely to be involved. The molecular identity of the underlying protein is not yet known; however, the relationship of several proteins suggested to be involved with volume regulatory response to VRAC is discussed.

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