Noxiustoxin, a short-chain toxin from the Mexican scorpion Centruroides noxius, induces transmitter release by blocking K+ permeability.
Noxiustoxin (NTX), a 39 amino acid peptide purified from the venom of the Mexican scorpion Centruroides noxius, has been shown to block voltage-dependent K+ currents in the squid giant axon (Possani et al., 1982; Carbone et al., 1982). Although several other drugs known as K+ channel blockers in the squid axon also act on isolated nerve terminals to produce an increase in transmitter release, these releasing effects have not been shown to be related to a decrease of K+ permeability in synaptosomes (Vizi et al., 1977; Tapia and Sitges, 1982). In this work we show that NTX increases 3H-GABA release from perfused mouse brain synaptosomes. This effect was not blocked by TTX. Ca2+ channel blockers (verapamil or Co2+) or the absence of external Ca2+ prevents the releasing effect of this toxin. NTX does not seem to induce transmitter release by directly increasing Ca2+ permeability: The K+ ionophore valinomycin completely inhibits the release induced by NTX, as well as that evoked by the K+ channel blocker 4-aminopyridine; in contrast, the release evoked by a Ca2+ ionophore is not blocked by valinomycin. These findings strongly suggest that the releasing effect of NTX is mediated by a decrease in K+ permeability. External Ca2+ is needed only in order to couple this stimulus with the release process. Consistent with this hypothesis, we present evidence that NTX blocks the efflux of 86Rb+ from synaptosomes. An extended comparison of the effect of 4-aminopyridine with that of NTX is also reported.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004594:Electrophysiology / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011188:Potassium / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000631:Aminopyridines; D012604:Scorpion Venoms; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; D011188:Potassium