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The Journal of Neuroscience, August 1, 2001, 21(15):5429-5438
Kir4.1 Potassium Channel Subunit Is Crucial for Oligodendrocyte
Development and In Vivo Myelination
Clemens
Neusch1,
Nora
Rozengurt2,
Russell E.
Jacobs1,
Henry A.
Lester1, and
Paulo
Kofuji3
1 Division of Biology, California Institute of
Technology, Pasadena, California 91125, 2 Department of
Pathology, University of California Los Angeles School of Medicine, Los
Angeles, California 90095, and 3 Department of
Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455
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.
Key words:
oligodendrocytes; myelination; inwardly rectifying
potassium channels; knock-out mouse; glia; spinal cord
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155429-10$05.00/0
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