BASIC-a bile acid-sensitive ion channel highly expressed in bile ducts

Brain liver intestine Na+ channel (BLINaC) is an ion channel of the DEG/ENaC gene family of unknown function. BLINaC from rats (rBLINaC) and humans (INaC) is inactive at rest, and its mode of activation has remained unclear. Here, we show that the BLINaC protein localizes to cholangiocytes, epithelial cells that line bile ducts. Moreover, we provide evidence that rBLINaC and INaC are robustly activated by bile acids, in particular chenodeoxycholic acid and hyodeoxycholic acid (EC50 =2.1 +/- 0.05 mM). Thus, BLINaC appears to be an epithelial cation channel of bile ducts sensitive to physiological concentrations of bile acids. BLINaC is related to acid-sensing ion channels (ASICs) and to the epithelial Na+ channel (ENaC) and shares ligand activation with ASICs and epithelial localization with ENaC. Therefore, based on the close homology of BLINaC to ASICs and its activation by bile acids, we propose to rename BLINaC bile acid-sensitive ion channel (BASIC).-Wiemuth, D., Sahin, H., Falkenburger, B. H., Lefevre, C. M. T., Wasmuth, H. E., Grunder, S. BASIC-a bile acid-sensitive ion channel highly expressed in bile ducts. FASEB J. 26, 4122-4130 (2012). www.fasebj.org