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Slc26a11 is prominently expressed in the brain and functions as a chloride channel: expression in Purkinje cells and stimulation of V H⁺-ATPase

Pflugers Arch. 2013 Nov;465(11):1583-97. doi: 10.1007/s00424-013-1300-6. Epub 2013 Jun 4.

Abstract

SLC26A11 (human)/Slc26a11 (mouse), also known as kidney brain anion transporter (KBAT), is a member of the SLC26 anion transporter family and shows abundant mRNA expression in the brain. However, its exact cellular distribution and subcellular localization in the brain and its functional identity and possible physiological roles remain unknown. Expression and immunostaining studies demonstrated that Slc26a11 is abundantly expressed in the cerebellum, with a predominant expression in Purkinje cells. Lower expression levels were detected in hippocampus, olfactory bulb, cerebral cortex, and subcortical structures. Patch clamp studies in HEK293 cells transfected with mouse cDNA demonstrated that Slc26a11 can function as a chloride channel that is active under basal conditions and is not regulated by calcium, forskolin, or co-expression with cystic fibrosis transmembrane regulator. Single and double immunofluorescent labeling studies demonstrated the localization of vacuolar (V) H⁺-ATPase and Slc26a11 (KBAT) in the plasma membrane in Purkinje cells. Functional studies in HEK293 cells indicated that transfection with Slc26a11 stimulated acid transport via endogenous V H⁺-ATPase. We conclude that Slc26a11 (KBAT) is prominently distributed in output neurons of various subcortical and cortical structures in the central nervous system, with specific expression in Purkinje cells and that it may operate as a chloride channel regulating acid translocation by H⁺-ATPase across the plasma membrane and in intracellular compartments.

Publication types

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

MeSH terms

  • Animals
  • Anion Transport Proteins / genetics
  • Anion Transport Proteins / metabolism*
  • Calcium / pharmacology
  • Cell Membrane / metabolism
  • Cerebral Cortex / metabolism
  • Colforsin / pharmacology
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • HEK293 Cells
  • Hippocampus / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Olfactory Bulb / metabolism
  • Organ Specificity
  • Protein Transport
  • Proton-Translocating ATPases / metabolism*
  • Purkinje Cells / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sulfate Transporters

Substances

  • Anion Transport Proteins
  • RNA, Messenger
  • Slc26a4 protein, mouse
  • Sulfate Transporters
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Colforsin
  • Proton-Translocating ATPases
  • Calcium