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,
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.
Keywords: Calcium channel, Cell culture, N-methyl-d-aspartate
(NMDA), Kainate, Energy