Alpha- 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 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.
Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte-MG, Brazil.
A R
AR
Massensini
T
T
Moraes-Santos
M V
MV
Gomez
M A
MA
Romano-Silva
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051381:Rats; D012604:Scorpion Venoms / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D002121:Calcium Channel Blockers; D012604:Scorpion Venoms; D018698:Glutamic Acid; D012964:Sodium; D002118:Calcium