Chloride Channel Protein 2 (CLCN2)

CLC2 chloride channels are expressed in epithelia affected by cystic fibrosis (CF) and raised the possibility that these might represent an alternative target for pharmacotherapy of CF. The explore this possibility, they manipulated genetically the expression levels of CLC2 channels in airway epithelial cells derived from cystic fibrosis patients. Whole-cell patch-clamp analysis of cells overexpressing CLC2 identified hyperpolarization-activated chloride ion currents (HACCs) that displayed time- and voltage-dependent activation and an inwardly rectifying steady-state current voltage relationship. Reduction of extracellular pH to 5.0 caused significant increases in HACCs in overexpressing cells and the appearance of robust currents in parental cells from the cystic fibrosis patient.