The ClC-3 chloride channels in cardiovascular disease.

ClC-3 is a member of the ClC voltage-gated chloride (Cl(-)) channel superfamily. Recent studies have demonstrated the abundant expression and pleiotropy of ClC-3 in cardiac atrial and ventricular myocytes, vascular smooth muscle cells, and endothelial cells. ClC-3 Cl(-) channels can be activated by increase in cell volume, direct stretch of β1-integrin through focal adhesion kinase and many active molecules or growth factors including angiotensin II and endothelin-1-mediated signaling pathways, Ca(2+)/calmodulin-dependent protein kinase II and reactive oxygen species. ClC-3 may function as a key component of the volume-regulated Cl(-) channels, a superoxide anion transport and/or NADPH oxidase interaction partner, and a regulator of many other transporters. ClC-3 has been implicated in the regulation of electrical activity, cell volume, proliferation, differentiation, migration, apoptosis and intracellular pH. This review will highlight the major findings and recent advances in the study of ClC-3 Cl(-) channels in the cardiovascular system and discuss their important roles in cardiac and vascular remodeling during hypertension, myocardial hypertrophy, ischemia/reperfusion, and heart failure.