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Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte Development and In Vivo Myelination

Neusch, Clemens and Rozengurt, Nora and Jacobs, Russell E. and Lester, Henry A. and Kofuji, Paulo (2001) Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte Development and In Vivo Myelination. Journal of Neuroscience, 21 (15). pp. 5429-5438. ISSN 0270-6474. PMCID PMC6762664. https://resolver.caltech.edu/CaltechAUTHORS:20160210-145519981

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Abstract

To understand the cellular and in vivo functions of specific K^+ channels in glia, we have studied mice with a null mutation in the weakly inwardly rectifying K^+ channel subunit Kir4.1. Kir4.1−/− mice display marked motor impairment, and the cellular basis is hypomyelination in the spinal cord, accompanied by severe spongiform vacuolation, axonal swellings, and degeneration. Immunostaining in the spinal cord of wild-type mice up to postnatal day 18 reveals that Kir4.1 is expressed in myelin-synthesizing oligodendrocytes, but probably not in neurons or glial fibrillary acidic protein-positive (GFAP-positive) astrocytes. Cultured oligodendrocytes from developing spinal cord of Kir4.1−/− mice lack most of the wild-type K^+ conductance, have depolarized membrane potentials, and display immature morphology. By contrast, cultured neurons from spinal cord of Kir4.1−/− mice have normal physiological characteristics. We conclude that Kir4.1 forms the major K^+ conductance of oligodendrocytes and is therefore crucial for myelination. The Kir4.1 knock-out mouse is one of the few CNS dysmyelinating or demyelinating phenotypes that does not involve a gene directly involved in the structure, synthesis, degradation, or immune response to myelin. Therefore, this mouse shows how an ion channel mutation could contribute to the polygenic demyelinating diseases.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/JNEUROSCI.21-15-05429.2001DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762664PubMed CentralArticle
ORCID:
AuthorORCID
Jacobs, Russell E.0000-0002-1382-8486
Lester, Henry A.0000-0002-5470-5255
Additional Information:© 2001 Society for Neuroscience. Beginning six months after publication the Work will be made freely available to the public on SfN’s website to copy, distribute, or display under a Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/). Received Jan. 12, 2001; revised May 8, 2001; accepted May 9, 2001. This work was supported by National Institutes of Health Grants GM-29836, EY12949, DA08944, and RR13625 and the Deutsche Forschungsgemeinschaft (NE-767/1-1). We thank S. S. Velan for help with the magnetic resonance imaging, S. McKinney for help with animals, V. Santoro for help in data analysis, and B. S. Khakh for comments.
Funders:
Funding AgencyGrant Number
NIHGM-29836
NIHEY12949
NIHDA08944
NIHRR13625
Deutsche Forschungsgemeinschaft (DFG)NE-767/1-1
Subject Keywords:oligodendrocytes; myelination; inwardly rectifying potassium channels; knock-out mouse; glia; spinal cord
Issue or Number:15
PubMed Central ID:PMC6762664
Record Number:CaltechAUTHORS:20160210-145519981
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160210-145519981
Official Citation:Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte Development and In Vivo Myelination Clemens Neusch, Nora Rozengurt, Russell E. Jacobs, Henry A. Lester, and Paulo Kofuji The Journal of Neuroscience, 1 August 2001, 21(15):5429-5438
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64387
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:10 Feb 2016 23:49
Last Modified:07 Oct 2019 14:55

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