CHLORIDE CONDUCTANCE AND SODIUM-DEPENDENT GLUCOSE-TRANSPORT IN RAT AND HUMAN ENTEROCYTES

Background & Aims: In cystic fibrosis intestine, there is an increase in the rate of Na+-dependent glucose absorption. This may result from enterocyte hyperpolarization after defective Cl- channel function, but only if Cl- secretion and Na+/glucose cotransport occur in the same m embrane. This study examined the effects of Cl- gradients on Na+/gluco se uptake in brush border membrane vesicles from rat and human small i ntestine. Methods: Vesicles were prepared by Mg2+-precipitation, and t he active uptake of tritiated glucose was measured using a filtration- stop protocol. Results: An outwardly directed Cl- gradient inhibited a ctive glucose uptake in rat vesicles, whereas an inward Cl- gradient s timulated uptake. These effects were sensitive to blockers of the cyst ic fibrosis transmembrane regulator but not to inhibitors of other Cl- channels. Active glucose uptake into vesicles prepared from normal hu man intestine was also inhibited by an outward Cl- gradient, whereas u ptake into vesicles prepared from a single sample of human cystic fibr osis intestine was not. Conclusions: A Cl- conductance resembling the cystic fibrosis transmembrane regulator is colocalized with Na+/glucos e cotransport in rat and human small intestine, supporting the possibi lity that abnormalities in glucose absorption in cystic fibrosis may b e a secondary effect of defects in Cl- channel function.