Excessive release of neurotransmitters is reported to contribute to the delayed neuronal death in animal models of cerebral ischemia. Since evidence is accumulating that N-type voltage-sensitive calcium channels (N-channels) regulate the release of neurotransmitters, we investigated the effects of ω-conotoxin GVIA (ω-CTX), an antagonist of N-channels, on delayed neuronal death following transient ischemia in gerbils. Delayed neuronal death in the CA1 subfield of the hippocampus following 5-min ischemia was attenuated by ω-CTX in a dose-dependent manner when the agent was injected intracisternally 1 hr before ischemia was produced. However, ω-CTX failed to prevent neurotoxicity produced by a direct injection of quinolinic acid into the hippocampus in rats. These results suggest that ω-CTX has a neuroprotective effect against ischemie brain injury, which effect probably results from its inhibition of the excessive release of neurotransmitters, including excitatory amino acids, during ischemia.
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