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

Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1079-88. doi: 10.1152/ajpgi.00354.2006. Epub 2006 Dec 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiporters / deficiency
  • Antiporters / genetics
  • Antiporters / metabolism*
  • Bicarbonates / metabolism*
  • Cation Transport Proteins / metabolism
  • Chloride-Bicarbonate Antiporters / deficiency
  • Chloride-Bicarbonate Antiporters / genetics
  • Chloride-Bicarbonate Antiporters / metabolism*
  • Chlorides / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Diffusion Chambers, Culture
  • Duodenum / cytology
  • Duodenum / metabolism*
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / 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

Substances

  • 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