Volume-regulated chloride channels and cerebral vascular remodelling.

1. Transmembrane Cl(-) transport through volume-regulated Cl(-) channels (VRCC) is implicated in cell cycle control and the proliferation of vascular smooth muscle cells (VSMC). In cerebrovascular VSMC, volume-regulated Cl(-) movement is enhanced with the severity of cerebrovascular remodelling induced by hypertension. 2. Expression of the ClC-3 chloride channel, a potential molecular candidate for the VRCC, is significantly increased with the progression of VSMC proliferation, but is decreased in apoptosis. 3. In the present review, we summarize recent findings regarding the functional role of volume-regulated ClC-3 chloride channels in VSMC proliferation, apoptosis and cerebrovascular remodelling during the development of hypertension. In addition, we discuss the relationship between the channel and intracellular signalling pathways, including the production of reactive oxygen species and the phosphorylation of Akt. 4. Recent studies strongly suggest that VRCC/ClC-3 is involved in the regulation of both cell proliferation and apoptosis. These findings suggest that ClC-3 chloride channels may be potential new targets for the prevention of the cerebrovascular remodelling that occurs during the development of hypertension.