Open AccessRole of Glutamate Receptors and Voltage-Dependent Calcium Channels in Glutamate Toxicity in Energy-Compromised Cortical Neurons
Author(s) -
M. Kimura,
Kouichi Katayama,
Yuji Nishizawa
Publication year - 1999
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.80.351
Subject(s) - nmda receptor , kainate receptor , glutamate receptor , neuroprotection , pharmacology , channel blocker , calcium channel , agonist , chemistry , voltage dependent calcium channel , calcium channel blocker , calcium , neurotoxicity , dizocilpine , ampa receptor , receptor , biology , toxicity , biochemistry , organic chemistry
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 N-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. NMDA-or 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, omega-agatoxin IVA and omega-agatoxin TK, and an N-type calcium channel blocker, omega-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.