Abstract
The pancreatic duct epithelium secretes the HCO3--rich pancreatic juice. The HCO3- transport across the luminal membrane has been proposed to be mediated by SLC26A Cl--HCO3- exchangers. To examine the electrophysiological properties of Cl--HCO3- exchangers, we directly measured HCO3- conductance in the luminal membrane of the interlobular pancreatic duct cells from guinea pigs using an inside-out patch-clamp technique. Intracellular HCO3- increased the HCO3- conductance with a half-maximal effective concentration value of approximately 30 mM. The selectivity sequence based on permeability ratios was SCN- (1.4) > Cl- (1.2) = gluconate (1.1) = I- (1.1) = HCO3- (1.0) > methanesulfonate (0.6). The sequence of the relative conductance was HCO3- (1.0) > SCN- (0.7) = I- (0.7) > Cl- (0.5) = gluconate (0.4) > methanesulfonate (0.2). The current dependent on intracellular HCO3- was reduced by replacement of extracellular Cl- with gluconate or by H2DIDS, an inhibitor of Cl--HCO3- exchangers. RT-PCR analysis revealed that the interlobular and main ducts expressed all SLC26A family members except Slc26a5 and Slc26a8. SLC26A1, SLC26A4, SLC26A6, and SLC26A10 were found to be localized to the luminal membrane of the guinea pig pancreatic duct by immunohistochemistry. These results demonstrate that these SLC26A Cl--HCO3- exchangers may mediate the electrogenic HCO3- transport through the luminal membrane and may be involved in pancreatic secretion in guinea pig ducts.