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Slc26a3(Down‐regulated in adenoma) Cl/HCO3 exchanger is responsible for Cl absorption and HCO3 secretion in the murine large intestine

In the large intestine a Cl/HCO3 exchanger is suggested to be involved in Cl absorption which is closely associated with Na absorption mediated by Na/H exchanger. A Cl/HCO3 exchanger is also responsible for HCO3 secretion. Molecular identity of these Cl/HCO3 exchanger(s) was investigated using mice with gene‐targeted knockout (KO) of Cl/HCO3 exchangers: Slc26a3, down‐regulated in adenoma (Dra). Isolated cecum and distal colon were mounted in Ussing chambers. We measured transepithelial fluxes of 22Na and 36Cl, and by using a pH‐stat device a luminal alkalinization rate. Essentially similar findings were obtained for both the cecum and distal colon. In control (ddy strain) and wild type mice, mucosa‐to‐serosa flux (Jms) was larger than serosa‐to‐mucosa flux (Jsm) for both 22Na and 36Cl. In contrast, in DraKO mice Jms and Jsm for 36Cl were both markedly reduced and net 36Cl absorption was almost, if not entirely, abolished, while Jms and Jsm for 22Na were not noticeably affected. Cl‐dependent HCO3 secretion was completely abolished in DraKO mice. These results suggest that, under Ussing chamber condition, Dra is a major transporter responsible for both the absorptive and secretory transport of Cl, and for most of the net Cl absorption. Dra is also involved in Cl‐dependent HCO3 secretion.