Cell volume-sensitive chloride channels: phenotypic properties and molecular identity.

Cell volume regulation is essential for the survival of cells. After osmotic swelling, animal cells show a regulatory volume decrease by releasing intracellular K(+), Cl (-)and water. In most cell types, volume-regulatory Cl(-) efflux is induced by activation of electroconductive anion pathways. Among these volume-activated Cl(-) channels, the most important and specific is a volume-sensitive outwardly rectifying (VSOR) Cl(-) channel. The phonotypical properties have been well described. Extracellular application of anionic forms of ATP and glibenclamide give rise to voltage-dependent open-channel block of this channel, the fact suggesting that its outer vestibule and pore are larger and smaller, respectively, than the sizes of ATP and glibenclamide. Consistent with this prediction, the pore radius of VSOR Cl(-) channel (0.63 nm) which has been recently determined is slightly smaller than the radii of ATP and glibenclamide. The activities of VSOR Cl(-) channels are implicated not only in regulatory volume decrease but also in many other physiological or pathophysiological cell events including cell death induction. Despite their ubiquitous expression and physiological/ pathophysiological significance, there is still a paucity of the molecular information of the VSOR Cl(-) channel.