抄録
Pancreatic duct cells produce HCO3−-rich isotonic fluid secretion. HCO3− transport across the apical membrane are thought to be mediated by CFTR and SLC26 anion transporters. We previously examined changes in pHi upon removal and restoration of luminal Cl− in the presence of HCO3− in interlobular pancreatic ducts isolated from slc26a6 null mice. In slc26a6 null ducts, HCO3−-efflux mode of apical [Cl−]o-[HCO3−]i exchange was decreased while HCO3−-influx mode of apical [Cl−]i-[HCO3−]o exchange was increased, suggesting the uni-directionality of slc26a6-mediated HCO3− transport. To investigate the stoichiometry of slc26a6 Cl−-HCO3− exchange, we examined net transport of HCO3− and Cl− by measuring luminal pH (pHL) and fluid secretory rate in sealed ducts of which the lumen was injected with BCECF-dextran. Duct lumen was filled with HCO3−-free, Cl−-rich (150 mM) solution and the superfusate was switched from the HCO3−-free, Cl−-rich solution to the standard HCO3−-buffered solution. This protocol would instantaneously generate a favorable gradient for apical Cl−-HCO3− exchange. Switching the superfusate caused transient decrease of pHL (CO2 diffusion) followed by continuous increase due to HCO3− secretion. The changes in pHL were accompanied with transient increase of fluid secretory rate in wild-type ducts, while transient fluid absorption was observed in most of slc26a6 null ducts. Calculation of net HCO3− and Cl− fluxes assuming ([HCO3−] + [Cl−] = 150 mM) suggests that slc26a6 mediates 1Cl−-2HCO3− exchange and that a 2Cl−-1HCO3− exchanger is up-regulated in slc26a6 null ducts. [J Physiol Sci. 2008;58 Suppl:S54]
