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Expression of Non-NMDA Glutamate Receptor Channel Genes by Clonal Human Neurons

Authors

  • Mattie Hardy,

    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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  • Donald Younkin,

    Corresponding author
    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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  • Cha-Min Tang,

    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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    • The present address for Dr. C.-M. Tang and Dr. Q.-Y. Shi is Department of Neurology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD, 21201, U.S.A.

  • Jeanette Pleasure,

    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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  • Qing-Yao Shi,

    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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    • The present address for Dr. C.-M. Tang and Dr. Q.-Y. Shi is Department of Neurology, University of Maryland School of Medicine, 10 South Pine Street, Baltimore, MD, 21201, U.S.A.

  • Margaret Williams,

    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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  • David Pleasure

    1. Division of Neurology Research, Children's Hospital of Philadelphia; and the Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, U.S.A.
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Address correspondence and reprint requests to Dr. D. Younkin at Division of Neurology Research, Children's Hospital of Philadelphia, Philadelphia, PA 19104, U.S.A.

Abstract

Abstract: Treatment of the human teratocarcinoma line NTera2/c1.D1 (NT2) with retinoic acid induces terminal neuronal differentiation. In a previous study, we found that the neurons obtained in this way express functional N-methyl-d-aspartate (NMDA) and non-NMDA glutamate receptor channels. We now show by reverse transcriptase-polymerase chain reaction and Southern blotting that these neurons transcribe each of the nine known non-NMDA glutamate receptor genes (GluR1-7, Ka-1, and Ka-2) and that four of these genes (GluR2, GluR6, GluR7, and Ka-1) are also transcribed by undifferentiated NT2 cells. Patch clamp studies demonstrate that individual non-NMDA glutamate receptor channels are readily isolated from NT2-derived neurons and that these channels are potently modulated by the desensitization blocker cyclothiazide. NT2-derived neurons are susceptible to kainate excitotoxicity but are not injured by prolonged exposure to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. We expect that the NT2-derived human neuronal culture system will facilitate studies of human neuronal non-NMDA glutamate receptor channels and of the pathophysiology of neuronal excitotoxicity.

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