Alpha- and beta-scorpion toxins evoke glutamate release from rat cortical synaptosomes with different effects on...

Scorpion toxins have long been used as tools in the investigation of neurotransmitter release mechanisms. We have used rat cortical synaptosomes to study the effects of a beta-type scorpion toxin (TiTX-gamma) on the release of glutamate and on the concentrations of free sodium and calcium ions inside the synaptosomes. The effects are compared with those of an alpha-type scorpion toxin (TsTX), on which there have been more studies. TsTX increased overall internal sodium and calcium ion concentrations and glutamate release in an incremental, dose dependent manner. TiTX-gamma similarly evoked glutamate release in an incremental, dose dependent manner. However, TiTX-gamma caused little increase in the overall internal sodium and calcium ion concentrations at low doses that evoked a significant release of glutamate and a maximal increase in these ions at somewhat higher doses. The results suggest that TiTX-gamma preferentially binds sodium channels close to the active zones for glutamate release and indicates that modifications of the activation or inactivation of the Na+-channel can lead to very different changes in the cytosolic concentrations of free Na+and Ca2+, with consequences for neurotransmission. This provides an interesting perspective concerning modulation of neurotransmitter release via pharmacological manipulation of Na+-channel properties, that may lead to a better comprehension of its physiological and pathological roles.