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

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 expl ores the nature of the coupling of Cl and Na/H exchange. A concentration of 100 mu M 5-nitro-2-(3-phenylpropylamino)benzoic acid, a Cl channel blocker , inhibited the Cl dependence of both proton gradient-driven Na-22 uptake f rom crypt cell apical membrane vesicles and Na-dependent intracellular pH r ecovery from an acid load during microperfusion of the crypt lumen. Cl-depe ndent proton gradient-driven Na-22 uptake was inhibited by 94% by 500 mu M DIDS but only by 1% by 10 mu M DIDS, an anion exchange inhibitor at low con centrations but a Cl channel blocker at high concentrations. In addition, a polyclonal antibody to the cystic fibrosis transmembrane conductance regul ator (CFTR) inhibited Cl-dependent proton gradient-driven 22Na uptake by 38 %. These results indicate that the Cl dependence of Na/H exchange in the co lonic crypt apical membrane involves a Cl channel and not a Cl/anion exchan ge and permit the speculation that this Cl channel activity represents both CFTR and the outward rectifying Cl conductance.