Aims:  The apical membrane anion exchanger putative anion transporter‐1 (Pat‐1) is expressed at significant levels in the lower villus epithelium of murine duodenum. However, previous studies of Cl⁻/HCO₃⁻ exchange in the lower villus have failed to demonstrate Pat‐1 function. Those studies routinely included luminal glucose which induces Na⁺‐coupled glucose transport and acidifies the villus epithelium. Since Pat‐1 has been proposed to be an electrogenic 1Cl⁻/2HCO₃⁻ exchanger, membrane depolarization or cell acidification during glucose transport may obscure Pat‐1 activity. Therefore, we investigated the effects of luminal glucose on Cl⁻_IN/HCO₃⁻_OUT exchange activity in the lower villus epithelium.

Methods:  Cl⁻_IN/HCO₃⁻_OUT exchange of villus epithelium in duodenal mucosa from Pat‐1 knockout (KO), Slc26a3 [down‐regulated in adenoma (Dra)] KO, cystic fibrosis transmembrane conductance regulator (Cftr) KO and wild‐type (WT) littermate mice was measured using the pH‐sensitive dye 2′,7′‐bis‐(2‐carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein. Short‐circuit current (I_sc) was measured in Ussing chambers.

Results:  During glucose absorption, Cl⁻_IN/HCO₃⁻_OUT exchange in the lower villus epithelium was abolished in the Dra KO and unaffected in the Pat‐1 KO relative to WT. However, during electroneutral mannose absorption or electrogenic α‐D‐methyl glucoside absorption, Cl⁻_IN/HCO₃⁻_OUT exchange was reduced in both Pat‐1 KO and Dra KO villi. Exposure to high [K⁺] abolished Cl⁻_IN/HCO₃⁻_OUT exchange in the Dra KO but not the Dra/Cftr double KO epithelium, suggesting that Pat‐1 activity is little affected by membrane depolarization except in the presence of Cftr.

Conclusions:  The metabolic and electrogenic activity of glucose transport obscures Cl⁻_IN/HCO₃⁻_OUT exchange activity of Pat‐1 in the lower villus. The inhibitory effects of membrane depolarization on Pat‐1 Cl⁻_IN/HCO₃⁻_OUT exchange may require concurrent membrane association with Cftr.