Details

Autor(en) / Beteiligte

• Walker, N. M.
• Simpson, J. E.
• Hoover, E. E.
• Brazill, J. M.
• Schweinfest, C. W.
• Soleimani, M.
• Clarke, L. L.

Titel

Functional activity of Pat-1 (Slc26a6) Cl−/HCO3− exchange in the lower villus epithelium of murine duodenum

Ist Teil von

• Acta Physiologica, 2011-01, Vol.201 (1), p.21-31

Ort / Verlag

Oxford, UK: Blackwell Publishing Ltd

Erscheinungsjahr

2011

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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 (Isc) 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.