Effects of Slc26a6 deletion and CFTR inhibition on HCO3- secretion by mouse pancreatic duct.

Pancreatic duct epithelium secretes HCO(3)(-)-rich fluid, which is dependent on cystic fibrosis transmembrane conductance regulator (CFTR). HCO(3)(-) transport across the apical membrane is thought to be mediated by both SLC26A6 Cl(-)-HCO(3)(-) exchange and CFTR HCO(3)(-) conductance. In this study we examined the relative contribution and interaction of SLC26A6 and CFTR in apical HCO(3)(-) transport. Interlobular pancreatic ducts were isolated from slc26a6 null mice. Intracellular pH (pH(i)) was measured by BCECF microfluorometry. Duct cells were stimulated with forskolin and alkalinized by acetate pre-pulse in the presence of HCO(3)(-)-CO(2). Apical HCO(3)(-) secretion was estimated from the recovery rate of pH(i) from alkaline load. When the lumen was perfused with high-Cl(-) solution, the rate of apical HCO(3)(-) secretion was increased by luminal application of CFTRinh-172 in ducts from wild-type mice but it was decreased in ducts from slc26a6 -/- mice. This suggests that slc26a6 and CFTR compensate/compete with each other for apical HCO(3)(-) secretion with high Cl(-) in the lumen. With high HCO(3)(-) in the lumen, luminal CFTRinh-172 reduced the rate of apical HCO(3)(-) secretion in both wild-type and slc26a6 -/- ducts. This suggests that HCO(3)(-) conductance of CFTR mediates a significant portion of apical HCO(3)(-) secretion with high HCO(3)(-) in the lumen.