PnTx3-6 a spider neurotoxin inhibits K+-evoked increase in [Ca2+]i and Ca2+-dependent glutamate release in synaptosomes

The present experiments investigated the effect of a neurotoxin purified from the venom of the spider Phoneutria nigriventer. This toxic component, P. nigriventer toxin 3-6 (PnTx3-6), abolished Ca2+-dependent glutamate release with an IC50 of 74.4 nM but did not alter Ca2+-independent secretion of glutamate when brain cortical synaptosomes were depolarized by KCl (33 mM). This effect was most likely due to interference with the entry of calcium through voltage activated calcium channels (VACC), reducing the increase in the intrasynaptosomal free calcium induced by membrane depolarization with an IC50 of 9.5 nM. We compared the alterations induced by PnTx3-6 with the actions of toxins known to block calcium channels coupled to exocytosis. Our results indicate that PnTx3-6 inhibition of glutamate release and intrasynaptosomal calcium involves P/Q type calcium channels and this toxin can be a valuable tool in the investigation of calcium channels. (C) 2002 Elsevier Science Ltd. All rights reserved.