PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of the murine duodenum.

Abstract

Basal HCO(3)(-) secretion across the duodenum has been shown in several species to principally involve the activity of apical membrane Cl(-)/HCO(3)(-) exchanger(s). To investigate the identity of relevant anion exchanger(s), experiments were performed using wild-type (WT) mice and mice with gene-targeted deletion of the following Cl(-)/HCO(3)(-) exchangers localized to the apical membrane of murine duodenal villi: Slc26a3 [down-regulated in adenoma (DRA)], Slc26a6 [putative anion transporter 1 (PAT-1)], and Slc4a9 [anion exchanger 4 (AE4)]. RT-PCR of the isolated villous epithelium demonstrated PAT-1, DRA, and AE4 mRNA expression. Using the pH-sensitive dye BCECF, anion exchange rates were measured across the apical membrane of epithelial cells in the upper villus of the intact duodenal mucosa. Under basal conditions, Cl(-)/HCO(3)(-) exchange activity was reduced by 65-80% in the PAT-1(-) duodenum, 30-40% in the DRA(-) duodenum, and <5% in the AE4(-) duodenum compared with the WT duodenum. SO(4)(2-)/HCO(3)(-) exchange was eliminated in the PAT-1(-) duodenum but was not affected in the DRA(-) and AE4(-) duodenum relative to the WT duodenum. Intracellular pH (pH(i)) was reduced in the PAT-1(-) villous epithelium but increased to WT levels in the absence of CO(2)/HCO(3)(-) or during methazolamide treatment. Further experiments under physiological conditions indicated active pH(i) compensation in the PAT-1(-) villous epithelium by combined activities of Na(+)/H(+) exchanger 1 and Cl(-)-dependent transport processes at the basolateral membrane. We conclude that 1) PAT-1 is the major contributor to basal Cl(-)/HCO(3)(-) and SO(4)(2-)/HCO(3)(-) exchange across the apical membrane and 2) PAT-1 plays a role in pH(i) regulation in the upper villous epithelium of the murine duodenum.

• Authors: Janet E Simpson, Clifford W Schweinfest, Gary E Shull, Lara R Gawenis, Nancy M Walker, Kathryn T Boyle, Manoocher Soleimani, Lane L Clarke
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 292 Issue 4 Pg. G1079-88 (Apr 2007) ISSN: 0193-1857 [Print] United States
• PMID: 17170027 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antiporters
• Bicarbonates
• Cation Transport Proteins
• Chloride-Bicarbonate Antiporters
• Chlorides
• Membrane Proteins
• RNA, Messenger
• Slc26a3 protein, mouse
• Slc26a6 protein, mouse
• Slc4a9 protein, mouse
• Slc9a1 protein, mouse
• Sodium-Hydrogen Exchanger 1
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers
• Sulfate Transporters
• Sulfates
• Cystic Fibrosis Transmembrane Conductance Regulator

Topics

• Animals
• Antiporters (deficiency, genetics, metabolism)
• Bicarbonates (metabolism)
• Cation Transport Proteins (metabolism)
• Chloride-Bicarbonate Antiporters (deficiency, genetics, metabolism)
• Chlorides (metabolism)
• Cystic Fibrosis Transmembrane Conductance Regulator (metabolism)
• Diffusion Chambers, Culture
• Duodenum (cytology, metabolism)
• Gene Expression
• Hydrogen-Ion Concentration
• Intestinal Mucosa (cytology, metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Knockout
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sodium-Hydrogen Exchanger 1
• Sodium-Hydrogen Exchanger 3
• Sodium-Hydrogen Exchangers (metabolism)
• Sulfate Transporters
• Sulfates (metabolism)
• Time Factors
• Tissue Culture Techniques