Release of neurotransmitters and depletion of synaptic vesicles in cerebral cortex slices by alpha-latrotoxin from black widow spider venom.

The effect of alpha-latrotoxin on cerebral cortex slices was studied by both biochemical and morphological methods. This toxin greatly stimulates the release of preloaded gamma-amino[3H]butyric acid from cortex slices. The response increases linearly with dose. The release is not dependent on the presence of extracellular Ca2+, and therefore it is not mediated by the release of other transmitters from other types of neurons. In contrast, no significant increase in the release of a nontransmitter substance alpha-amino[14C]isobutyric acid is observed. Since previously we have shown that alpha-latrotoxin stimulated the release of acetylcholine and norepinephrine from cortex slices, it appears that the toxin probably selectively releases all neurotransmitters. The toxin also profoundly depletes the synaptic vesicle population in boutons in the cortex slices. The results suggest that the release of neurotransmitter and the depletion of synaptic vesicle in boutons are manifestations of a single action of the toxin. Therefore, alpha-latrotoxin can be used as a good tool for the identification of neurotransmitters and in studies on the mechanism of neurotransmitter release.