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Am J Physiol Gastrointest Liver Physiol 276: G73-G78, 1999;
0193-1857/99 $5.00
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Vol. 276, Issue 1, G73-G78, January 1999

Role of Cl channels in Cl-dependent Na/H exchange

Vazhaikkurichi M. Rajendran, John Geibel, and Henry J. Binder

Departments of Internal Medicine, Surgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8019

A novel Na/H exchange activity that requires Cl was recently identified in the apical membrane of crypt cells of the rat distal colon. This study explores the nature of the coupling of Cl and Na/H exchange. A concentration of 100 µM 5-nitro-2-(3-phenylpropylamino)benzoic acid, a Cl channel blocker, inhibited the Cl dependence of both proton gradient-driven 22Na uptake from crypt cell apical membrane vesicles and Na-dependent intracellular pH recovery from an acid load during microperfusion of the crypt lumen. Cl-dependent proton gradient-driven 22Na uptake was inhibited by 94% by 500 µM DIDS but only by 1% by 10 µM DIDS, an anion exchange inhibitor at low concentrations but a Cl channel blocker at high concentrations. In addition, a polyclonal antibody to the cystic fibrosis transmembrane conductance regulator (CFTR) inhibited Cl-dependent proton gradient-driven 22Na uptake by 38%. These results indicate that the Cl dependence of Na/H exchange in the colonic crypt apical membrane involves a Cl channel and not a Cl/anion exchange and permit the speculation that this Cl channel activity represents both CFTR and the outward rectifying Cl conductance.

colonic crypt glands; apical membrane vesicles; cystic fibrosis transmembrane conductance regulator; outward rectifying chloride conductance


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