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 Ca(2+)-dependent glutamate release with an IC(50) of 74.4nM but did not alter Ca(2+)-independent secretion of glutamate when brain cortical synaptosomes were depolarized by KCl (33mM). 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 IC(50) of 9.5nM. 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.
Vieira
Luciene B
LB
Laboratório de Neurofarmacologia, Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Caixa Postal 2486, 31270-901 Belo Horizonte, MG, Brazil.
Kushmerick
C
C
Reis
Helton J
HJ
Diniz
Carlos R
CR
Cordeiro
Marta N
MN
Prado
Marco A M
MA
Kalapothakis
E
E
Romano-Silva
Marco A
MA
Gomez
Marcus V
MV
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000302:isolation & purification / Q000494:pharmacology*; D011188:Potassium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D009479:Neuropeptides; C098736:Tx3 neurotoxin; D018698:Glutamic Acid; D011188:Potassium; D002118:Calcium