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

Pancreatic duct epithelium secretes HCO3 - -rich fluid, which is dependent on cystic fibrosis transmembrane conductance regulator (CFTR). HCO3 - transport across the apical membrane is thought to be mediated by both SLC26A6 Cl - -HCO3 - exchange and CFTR HCO3 - conductance. In this study we examined the relative contribution and interac- tion of SLC26A6 and CFTR in apical HCO3 - transport. Interlobular pancreatic ducts were isolated from slc26a6 null mice. Intracellular pH (pHi) was measured by BCECF micro- fluorometry. Duct cells were stimulated with forskolin and alkalinized by acetate pre-pulse in the presence of HCO3 - -CO2 .A pical HCO3 - secretion was estimated from the recovery rate of pHi from alkaline load. When the lumen was perfused with high-Cl - solution, the rate of apical HCO3 - 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 sug- gests that slc26a6 and CFTR compensate/compete with each other for apical HCO3 - se- cretion with high Cl - in the lumen. With high HCO3 - in the lumen, luminal CFTRinh-172 reduced the rate of apical HCO3 - secretion in both wild-type and slc26a6 -/- ducts. This sug- gests that HCO3 - conductance of CFTR mediates a significant portion of apical HCO3 - secre- tion with high HCO3 - in the lumen. J. Med. Invest. 56 Suppl. : 332-335, December, 2009