Chloride voltage-gated channel 2 (ClC-2)

Chloride voltage-gated channel 2 (ClC-2) is a ubiquitously expressed member of the CLC family of chloride channels, encoded by the CLCN2 gene. It primarily functions as a plasma membrane chloride channel that is activated by hyperpolarization, cell swelling, and acidic pH, playing a vital role in regulating cell volume and chloride homeostasis across various tissues (UniProt ID: Q92496). In the gastrointestinal tract, ClC-2 is located on the apical membrane of epithelial cells, where its activation promotes the secretion of chloride ions and water into the lumen, making it a key target for treating chronic constipation and irritable bowel syndrome (PubMed: 19543360). Mutations in the CLCN2 gene are associated with leukoencephalopathy with ataxia, a rare neurological disorder, highlighting its importance in maintaining central nervous system integrity (StatPearls). Pharmacologically, ClC-2 is most notably targeted by lubiprostone, a bicyclic fatty acid derivative that acts as a selective activator to enhance intestinal motility without affecting systemic electrolyte levels significantly (PubChem).

Other names

CLCN2Chloride channel protein 2CIC-2Voltage-gated chloride channel 2

Activation of ClC-2 on the apical membrane of the gastrointestinal epithelium to increase chloride-rich fluid secretion into the intestinal lumen, thereby facilitating bowel movement.