Electrophysiological properties of anion exchangers in the luminal membrane of guinea pig pancreatic duct cells

The pancreatic duct epithelium secretes the HCO(3)(−)-rich pancreatic juice. The HCO(3)(−) transport across the luminal membrane has been proposed to be mediated by SLC26A Cl(−)–HCO(3)(−) exchangers. To examine the electrophysiological properties of Cl(−)–HCO(3)(−) exchangers, we directly measured HCO(3)(−) conductance in the luminal membrane of the interlobular pancreatic duct cells from guinea pigs using an inside-out patch-clamp technique. Intracellular HCO(3)(−) increased the HCO(3)(−) 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) = HCO(3)(−) (1.0) > methanesulfonate (0.6). The sequence of the relative conductance was HCO(3)(−) (1.0) > SCN(−) (0.7) = I(−) (0.7) > Cl(−) (0.5) = gluconate (0.4) > methanesulfonate (0.2). The current dependent on intracellular HCO(3)(−) was reduced by replacement of extracellular Cl(−) with gluconate or by H(2)DIDS, an inhibitor of Cl(−)–HCO(3)(−) 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(−)–HCO(3)(−) exchangers may mediate the electrogenic HCO(3)(−) transport through the luminal membrane and may be involved in pancreatic secretion in guinea pig ducts.