ALPHA-SCORPION AND BETA-SCORPION TOXINS EVOKE GLUTAMATE RELEASE FROM RAT CORTICAL SYNAPTOSOMES WITH DIFFERENT EFFECTS ON [NA+](I) AND [CA2+](I)

Scorpion toxins have long been used as tools in the investigation of n eurotransmitter release mechanisms. We have used rat cortical synaptos omes to study the effects of a beta-type scorpion toxin (TiTX-gamma) o n the release of glutamate and on the concentrations of free sodium an d calcium ions inside the synaptosomes. The effects are compared with those of an a-type scorpion toxin (TsTX), on which there have been mor e studies. TsTX increased overall internal sodium and calcium ion conc entrations and glutamate release in an incremental, dose dependent man ner. TiTX-gamma similarly evoked glutamate release in an incremental, dose dependent manner. However, TiTX-gamma caused little increase in t he 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 -y preferentially binds sodium channels close to the active zones for glutamate release and indicates that modifications of the activation o r inactivation of the Na+-channel can lead to very different changes i n the cytosolic concentrations of free Na+ and Ca2+, with consequences for neurotransmission. This provides an interesting perspective conce rning modulation of neurotransmitter release via pharmacological manip ulation of Na+-channel properties, that may lead to a better comprehen sion of its physiological and pathological roles. (C) 1998 Elsevier Sc ience Ltd. All rights reserved.