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.
All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience