Physiological characteristics and molecular identity of HCO_3-conductance in pancreatic duct cells.

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We have investigated molecular mechanisms for HCO_3-transport across the apical membrane of pancreatic duct cells using interlobular pancreatic duct segments isolated from guinea-pig and transgenic mice. As a clinical research, we examined polymorphisms of CFTR (cystic fibrosis transmembrane conductance regulator) in Japanese and established a simple method to measure concentration in sweat.1. Isolated pancreatic ducts from AF mice, a cystic fibrosis model that human AF508 mutation was introduced, had very poor capacity for cAMP-stimulated fluid secretion and stronger activity of of Na^+-H^+ exchange (NHE) in the apical membrane. The enhanced of apical NHE activity may be involved in decrease of pH and acidification of pancreatic juice.2. The HCO_3--influx mode of apical [CI^-]_i/[HCO_3^-]_o exchange was dramatically increased in slc26a6 null mice, whereas the HCO_3^--efflux mode of apical [C1^-]_i/[HCO_3^-]_o exchange was decreased in slc26a6 null mice, suggesting the uni-directionality of the slc26a6-mediated HCO_3" transport. When pure pancreatic juice was collected in vivo, neither juice volume nor its pH showed differences between WT and slc26a6 null mice.3. The electrogenic HCO_3^-transport (HCO_3^-conductance) across the apical membrane was demonstrated in luminally-perfused isolated pancreatic ducts as changes in intracellular pH induced by manipulation of bath K^+ concentration in the condition that basolateral HCO_3^-transport was inhibited. The apical HCO_3^- conductance was not dependent on and was abolished in isolated ducts from AF mice. The data suggest that CFTR works as a HCO_3" channel in pancreatic duct cells.