Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility
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 selec...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/34829 |
| _version_ | 1828166025434103808 |
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| author | Valerie A Larson Yevgeniya Mironova Kimberly G Vanderpool Ari Waisman John E Rash Amit Agarwal Dwight E Bergles |
| author_facet | Valerie A Larson Yevgeniya Mironova Kimberly G Vanderpool Ari Waisman John E Rash Amit Agarwal Dwight E Bergles |
| author_sort | Valerie A Larson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:54:41Z |
| format | Article |
| id | doaj.art-54e08819929b4b50910d9569327957e8 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:54:41Z |
| publishDate | 2018-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-54e08819929b4b50910d9569327957e82022-12-22T03:52:50ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.34829Oligodendrocytes control potassium accumulation in white matter and seizure susceptibilityValerie A Larson0https://orcid.org/0000-0003-0778-0305Yevgeniya Mironova1Kimberly G Vanderpool2Ari Waisman3John E Rash4Amit Agarwal5https://orcid.org/0000-0001-7948-4498Dwight E Bergles6https://orcid.org/0000-0002-7133-7378The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Biomedical Sciences, Colorado State University, Fort Collins, United StatesInstitute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, GermanyDepartment of Biomedical Sciences, Colorado State University, Fort Collins, United StatesThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesThe Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United StatesThe 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.https://elifesciences.org/articles/34829Kir4.1myelinseizurepotassiumoligodendrocyteepilepsy |
| spellingShingle | Valerie A Larson Yevgeniya Mironova Kimberly G Vanderpool Ari Waisman John E Rash Amit Agarwal Dwight E Bergles Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility eLife Kir4.1 myelin seizure potassium oligodendrocyte epilepsy |
| title | Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility |
| title_full | Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility |
| title_fullStr | Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility |
| title_full_unstemmed | Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility |
| title_short | Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility |
| title_sort | oligodendrocytes control potassium accumulation in white matter and seizure susceptibility |
| topic | Kir4.1 myelin seizure potassium oligodendrocyte epilepsy |
| url | https://elifesciences.org/articles/34829 |
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