Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility
- Johns Hopkins University School of Medicine, United States
- Colorado State University, United States
- Johannes Gutenberg University, Germany
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
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.
Reviewing Editor
- Gary L Westbrook, Vollum Institute, United States
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.
Version history
- Received: January 5, 2018
- Accepted: March 28, 2018
- Accepted Manuscript published: March 29, 2018 (version 1)
- 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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Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility
eLife 7:e34829.
https://doi.org/10.7554/eLife.34829
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