1. Neuroscience
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Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility

  1. Valerie A Larson
  2. Yevgeniya Mironova
  3. Kim G Vanderpool
  4. Ari Waisman
  5. John E Rash
  6. Amit Agarwal  Is a corresponding author
  7. Dwight E Bergles  Is a corresponding author
  1. Johns Hopkins University School of Medicine, United States
  2. Colorado State University, United States
  3. Johannes Gutenberg University, Germany
Research Article
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Cite this article as: eLife 2018;7:e34829 doi: 10.7554/eLife.34829

Abstract

The inwardly rectifying K+ channel Kir4.1 is broadly expressed by CNS glia and deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here we show that selective deletion of Kir4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not impair their development or disrupt the structure of myelin. However, mice lacking oligodendrocyte Kir4.1 channels exhibited profound functional impairments, including slower clearance of extracellular K+ and delayed recovery of axons from repetitive stimulation in white matter, as well as spontaneous seizures, a lower seizure threshold, and activity-dependent motor deficits. These results indicate that Kir4.1 channels in oligodendrocytes play an important role in extracellular K+ homeostasis in white matter, and that selective loss of this channel from oligodendrocytes is sufficient to impair K+ clearance and promote seizures.

Article and author information

Author details

  1. Valerie A Larson

    The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0778-0305
  2. Yevgeniya Mironova

    The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
  3. Kim G Vanderpool

    Department of Biological Sciences, Colorado State University, Fort Collins, United States
    Competing interests
    No competing interests declared.
  4. Ari Waisman

    Institute for Molecular Medicine, University Medical Center, Johannes Gutenberg University, Mainz, Germany
    Competing interests
    No competing interests declared.
  5. John E Rash

    Department of Biomedical Sciences, Colorado State University, Fort Collins, United States
    Competing interests
    No competing interests declared.
  6. Amit Agarwal

    The Solomon H Snyder Department of NeuroscienceInstitute for Anatomy and Cell Biology, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    agarwal@ana.uni-heidelberg.de
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7948-4498
  7. Dwight E Bergles

    The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    dbergles@jhmi.edu
    Competing interests
    Dwight E Bergles, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7133-7378

Funding

National Institutes of Health (NS080153)

  • John E Rash

Dr. Miriam and Sheldon G. Adelson Medical Research Foundation

  • Dwight E Bergles

Target ALS

  • Dwight E Bergles

National Institutes of Health (NS050274)

  • Dwight E Bergles

National Institutes of Health (NS051509)

  • Dwight E Bergles

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#MO14M310) of the Johns Hopkins University.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: January 5, 2018
  2. Accepted: March 28, 2018
  3. Accepted Manuscript published: March 29, 2018 (version 1)
  4. Version of Record published: April 17, 2018 (version 2)

Copyright

© 2018, Larson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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