Manami Kimura, Kouichi Katayama and Yukio Nishizawa (*)
Eisai Tsukuba Research Laboratories, 5 - 1 - 3 Tokodai, Tsukuba, Ibaraki 300 - 2635, Japan
(*) To whom correspondence should be addressed.
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. 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, É÷-agatoxin IVA and É÷-agatoxin TK, and an N-type calcium channel blocker, É÷-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.
Keywords: Calcium channel, Cell culture, N-methyl-d-aspartate (NMDA), Kainate, Energy