Molecular characterization of BASIC, an epithelial channel in the liver, and analysis of its physiological function.

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BLINaC (Brain-Liver-Intestine Na+ Channel) belongs to the DEG/ENaC family of ion channels. While the function and activation stimuli for many members of this channel family are well studied, very little is known about BLINaC. The expression of BLINaC mRNA was shown in the brain, the liver and the intestinal tract. By immunohistochemical means we were able to show that the channel is specifically localized to the apical region of cholangiocytes, the epithelial cells of the bile duct. Furthermore we were able to show that BLINaC is activated by bile acids which are present in bile ducts at high concentrations. Therefore we renamed the channel from BLINaC to BASIC - Bile Acid Sensing Ion Channel. The objective of the proposed project is the analysis of the physiological function of BASIC in cholangiocytes using electrophysiological techniques. Furthermore we want to characterize the mechanism underlying the activation of BASIC by bile acids and identify interaction partners of the channel to gain additional information on the physiological function of BASIC. The results of this project will significantly contribute towards elucidating the function of BASIC.