title: Modulation of Na+-channels by neurotoxins produces different effects on [3H]ACh release with mobilization of distinct Ca2+-channels.
abstract: 1. Voltage-gated Na+ channels are responsible for initiation and conduction of action potentials. The arrival of an action potential at nerve terminal increases intracellular Na+ and Ca2+ concentrations. Calcium entry into neurons through voltage-dependent calcium channels is associated with a variety of intracellular processes. Scorpion neurotoxins have been used as tools to investigate mechanisms involved in neurotransmitter release. Tityustoxin (TsTX) is an alpha-type toxin that delays Na+-channel inactivation. Toxin-gamma (TiTX-gamma) is a beta-type toxin that induces Na+-channel activation at resting potentials. 2. In the present work, we describe the effects of both toxins on [3H]acetylcholine ([3H]ACh) release from rat cerebrocortical synaptosomes, in the presence or absence of the calcium channels blockers: omega-conotoxin-GVIA (omega-CgTx), 1 microM; omega-agatoxin-IVA (omega-Aga), 30 nM; omega-conotoxin-MVIIC (omega-MVIIC), 1 microM; or verapamil, 1 microM. 3. TsTX evokes [3H]ACh release in a concentration-dependent manner with a gradual increase up to saturation at concentrations of 500 nM. However, release of ACh evoked by TiTX-gamma was not linear regarding the toxin concentration. The [3H]-ACh release evoked by TsTX or TiTX-gamma was partially inhibited by omega-CgTx or omega-Aga, and blocked with omega-MVIIC. Verapamil (1 microM) had no effect. Tetrodotoxin blocked [3H]ACh release evoked by both toxins. 4. These results show that different actions on Na+-channels produce different effects on [3H]ACh release with involvement of distinct presynaptic Ca2+-channels, which supports the idea that sodium channels may modulate neurotransmitter release.
authors.affiliation: Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Eduardo Belisário
authors.initials: EB
authors.lastname: Falqueto
authors.forename: André Ricardo
authors.initials: AR
authors.lastname: Massensini
authors.forename: Tasso
authors.initials: T
authors.lastname: Moraes-Santos
authors.forename: Marcus Vinícius
authors.initials: MV
authors.lastname: Gomez
authors.forename: Marco A
authors.initials: MA
authors.lastname: Romano-Silva
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D009498:Neurotoxins / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes; D014316:Tritium
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009498:Neurotoxins; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C119038:Ts-gamma neurotoxin; D014316:Tritium; D000109:Acetylcholine