Abstract
The nonselective anion exchanger Slc26a6, also known as putative anion transporter 1 and chloride/formate exchanger, is thought to play a major role in HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math> transport in exocrine glands. In this study, Slc26a6 null mice were used to explore the function of Slc26a6 in the exocrine pancreas. Slc26a6 primarily localized to the apical membrane of pancreatic exocrine acinar cells. The volume of stimulated juice secretion by the ex vivo pancreas was significantly reduced ~35% in Slc26a6-/- mice, but no changes occurred in the gross structure or gland weights of Slc26a6 null mice. The secretion of pancreatic juice by Slc26a6+/+ mice was dependent on HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math> while, in contrast, fluid secretion by Slc26a6-/- mice was independent of HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math>, suggesting that Slc26a6 mediates the HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math>-dependent component of fluid secretion. Consistent with these observations, disruption of Slc26a6 also significantly reduced HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math> secretion by the pancreas ~35%. Taken together, these results demonstrate that the apical Slc26a6 anion exchanger in acinar cells is involved in HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math>-dependent fluid secretion but that another major HCO−3HCO3-<math><mrow><msubsup><mrow><mtext>HCO</mtext></mrow><mn>3</mn><mo>-</mo></msubsup></mrow></math>-independent pathway is the primary driver of the fluid secretion process in the mouse pancreas.