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

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Author(s)

Abstract

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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 80(4), 351-358, 1999-08-01

    The Japanese Pharmacological Society

References:  42

Cited by:  4

Codes

  • NII Article ID (NAID)
    10008195828
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4837021
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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