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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

  • Ion channels, receptors and transporters
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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.

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Acknowledgments

The authors express appreciation to M. Rutteman and E. Haasdijk from Erasmus MC for their contribution and to Dr. D. Jaarsma from Erasmus and Dr. Masato Nakafuku, Professor of Pediatrics, Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, for their helpful discussions. These studies were supported by the Dutch Organization for Medical Sciences (ZonMw; CIDZ), DFG SFB699A7 (KK), National Institute of Health R56DK62809 (MS), Life Sciences (ALW; CIDZ), Senter (Neuro-Basic; CIDZ), Merit Review Award from the Department of Veterans Administration (MS), Prinses Beatrix Fonds (CIDZ), ERCadvanced, CEREBNET and C7 programs of the European Community (CIDZ), and funds from US Renal Care (MS) and Center on Genetics of Transport at University of Cincinnati (MS).

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Authors and Affiliations

  1. Department of Neuroscience, Erasmus University, Rotterdam, The Netherlands

    Negah Rahmati & Chris I. De Zeeuw

  2. Institut für Physiologie, Universität Regensburg, Regensburg, Germany

    Karl Kunzelmann & Lalida Sirianant

  3. Department of Medicine, University of Cincinnati, 231 Albert Sabin Way, MSB 6213, Cincinnati, OH, 45267-0585, USA

    Jie Xu, Sharon Barone & Manoocher Soleimani

  4. Netherlands Institute for Neuroscience, Royal Dutch Academy of Arts & Sciences, Amsterdam, The Netherlands

    Chris I. De Zeeuw

  5. Center on Genetics of Transport and Epithelial Biology, University of Cincinnati, Cincinnati, USA

    Manoocher Soleimani

  6. Veterans Administration Research Services, Cincinnati, USA

    Manoocher Soleimani

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  1. Negah Rahmati
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  2. Karl Kunzelmann
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  3. Jie Xu
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  4. Sharon Barone
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  6. Chris I. De Zeeuw
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  7. Manoocher Soleimani
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Correspondence to Chris I. De Zeeuw or Manoocher Soleimani.

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Rahmati, N., Kunzelmann, K., Xu, J. et al. 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 - Eur J Physiol 465, 1583–1597 (2013). https://doi.org/10.1007/s00424-013-1300-6

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  • DOI: https://doi.org/10.1007/s00424-013-1300-6

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