Effect of Slc26a6 deletion on apical Cl^-/HCO₃ ^- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct

The role of Slc26a6 (PAT1) on apical Cl^-/HCO₃ ^- exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT) mice. Apical Cl ^-/HCO₃^- exchange activity was measured with the pH-sensitive dye BCECF in microperfused interlobular ducts. The HCO ₃^--influx mode of apical [Cl^-] _i/[HCO₃^-]_o exchange (where brackets denote concentration and subscripts i and o denote intra- and extracellular, respectively) was dramatically upregulated in Slc26a6 null mice (P < 0.01 vs. WT), whereas the HCO₃^--efflux mode of apical [Cl ^-]_o/[HCO₃^-]_i exchange was decreased in Slc26a6 null mice (P < 0.05 vs. WT), suggesting the unidirectionality of the Slc26a6-mediated HCO₃^- transport. Fluid secretory rate in interlobular ducts were comparable in WT and Slc26a6 null mice (P > 0.05). In addition, when pancreatic juice was collected from whole animal in basal and secretin-stimulated conditions, neither juice volume nor its pH showed differences between WT and Slc26a6 null mice. Semi-quantitative RT-PCR demonstrated more than fivefold upregulation in Slc26a3 (DRA) expression in Slc26a6 knockout pancreas. In conclusion, these results point to the role of Slc26a6 in HCO₃^- efflux at the apical membrane and also suggest the presence of a robust Slc26a3 compensatory upregulation, which can replace the function of Slc26a6 in pancreatic ducts.