Role of Glutamate Receptors and Voltage-Dependent Calcium Channels in Glutamate Toxicity in Energy-Compromised Cortical Neurons

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We have examined the effect of glutamate receptor antagonists and voltage-dependent calcium channel blockers on the neuronal injury induced by the combination of a low concentration of <I>N</I>-methyl-D-aspartate (NMDA) or kainate and energy compromise resulting from the use of glucose-free incubation buffer. Toxicity induced by NMDA or kainate was enhanced in the glucose-free buffer. NMDAor non-NMDA-receptor antagonists added to the glucose-free buffer at the same time inhibited the neuronal cell death induced by each agonist. An NMDA-receptor antagonist, MK-801, but not non-NMDA-receptor antagonists, inhibited the toxicity when added to the culture medium after exposure of the cells to the agonists. P/Q-type calcium channel blockers, ω-agatoxin IVA and ω-agatoxin TK, and an N-type calcium channel blocker, ω-conotoxin GVIA, significantly attenuated the neuronal injury, although an L-type calcium channel blocker, nifedipine, showed little neuroprotective effect. A combination of calcium channel blockers of the three subtypes showed the most prominent neuroprotective effect. These observations suggest that the overactivation of NMDA and non-NMDA receptors and consequent activation of the voltage-dependent calcium channels lead to neuronal cell death in energy-compromised cortical neurons.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 80(4), 351-358, 1999-08-01

    公益社団法人 日本薬理学会

参考文献:  42件中 1-42件 を表示

被引用文献:  4件中 1-4件 を表示

各種コード

  • NII論文ID(NAID)
    10008195828
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4837021
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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