title: Role of glutamate receptors and voltage-dependent calcium channels in glutamate toxicity in energy-compromised cortical neurons.
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 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.
authors.affiliation: Eisai Tsukuba Research Laboratories, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Katayama
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D060848:Agatoxins; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D005333:Fetus; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000633:toxicity*; D007608:Kainic Acid / Q000633:toxicity; D016202:N-Methylaspartate / Q000633:toxicity; D018696:Neuroprotective Agents / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000502:physiology*; D013111:Spider Venoms / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
chemical_list: D060848:Agatoxins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D013111:Spider Venoms; C083855:omega-agatoxin-Aa4b; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D005947:Glucose; D007608:Kainic Acid