Slc26a6 is an apical membrane anion exchanger that drives HCO3--dependent fluid secretion in murine pancreatic acinar cells

Am J Physiol Cell Physiol. 2019 Dec 1;317(6):C1153-C1160. doi: 10.1152/ajpcell.00257.2019. Epub 2019 Sep 18.

Abstract

The nonselective anion exchanger Slc26a6, also known as putative anion transporter 1 and chloride/formate exchanger, is thought to play a major role in HCO3- transport in exocrine glands. In this study, Slc26a6 null mice were used to explore the function of Slc26a6 in the exocrine pancreas. Slc26a6 primarily localized to the apical membrane of pancreatic exocrine acinar cells. The volume of stimulated juice secretion by the ex vivo pancreas was significantly reduced ~35% in Slc26a6-/- mice, but no changes occurred in the gross structure or gland weights of Slc26a6 null mice. The secretion of pancreatic juice by Slc26a6+/+ mice was dependent on HCO3- while, in contrast, fluid secretion by Slc26a6-/- mice was independent of HCO3-, suggesting that Slc26a6 mediates the HCO3--dependent component of fluid secretion. Consistent with these observations, disruption of Slc26a6 also significantly reduced HCO3- secretion by the pancreas ~35%. Taken together, these results demonstrate that the apical Slc26a6 anion exchanger in acinar cells is involved in HCO3--dependent fluid secretion but that another major HCO3--independent pathway is the primary driver of the fluid secretion process in the mouse pancreas.

Keywords: Slc26a6; bicarbonate secretion; fluid secretion; pancreas.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Acinar Cells / cytology
  • Acinar Cells / metabolism*
  • Animals
  • Anoctamin-1 / genetics
  • Anoctamin-1 / metabolism
  • Antiporters / deficiency
  • Antiporters / genetics*
  • Aquaporin 5 / genetics
  • Aquaporin 5 / metabolism
  • Bicarbonates / metabolism*
  • Body Fluids / metabolism*
  • Body Weight
  • Cell Line
  • Cell Membrane / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Female
  • Gene Expression Regulation
  • Humans
  • Ion Transport
  • Male
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Organ Size
  • Pancreas, Exocrine / cytology
  • Pancreas, Exocrine / metabolism*
  • Solute Carrier Family 12, Member 2 / genetics
  • Solute Carrier Family 12, Member 2 / metabolism
  • Sulfate Transporters / deficiency
  • Sulfate Transporters / genetics*

Substances

  • ANO1 protein, mouse
  • Anoctamin-1
  • Antiporters
  • Aqp5 protein, mouse
  • Aquaporin 5
  • Bicarbonates
  • Cftr protein, mouse
  • Slc12a2 protein, mouse
  • Slc26a6 protein, mouse
  • Solute Carrier Family 12, Member 2
  • Sulfate Transporters
  • Cystic Fibrosis Transmembrane Conductance Regulator