Modulation of Na+-channels by neurotoxins produces different effects on [3H]ACh release with mobilization of distinct Ca2+-channels.
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.
Falqueto
Eduardo Belisário
EB
Laboratório de Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Massensini
André Ricardo
AR
Moraes-Santos
Tasso
T
Gomez
Marcus Vinícius
MV
Romano-Silva
Marco A
MA
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
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