Characterization of the actions of toxins II-9.2.2 and II-10 from the venom of the scorpion Centruroides noxius on transmitter release from mouse brain synaptosomes.
Toxic peptides II-9.2.2 and II-10, purified from Centruroides noxius venom, bear highly homologous N-terminal amino acid sequences, and both toxins are lethal to mice. However, only toxin II-10 is active on the voltage-clamped squid axon, selectively decreasing the voltage-dependent Na+ current. Here, we have tested toxins II-9 and II-10 on synaptosomes from mouse brain: both toxins increased the release of gamma-[3H]aminobutyric acid ([3H]GABA). Their effect was completely blocked by tetrodotoxin or by the absence of external Na+. Also, both toxins increased Na+ permeability in isolated nerve terminals. Besides the observation that toxin II-9 is active on synaptosomes, the effect of toxin II-10 in this preparation is opposite to that observed in the squid axon. Thus, our results reflect functional differences between the populations of Na+ channels in mouse brain synaptosomes and in the squid axon. The release of GABA evoked by these toxins from synaptosomes required external Ca2+ and was blocked by Ca2+ channel blockers (verapamil and Co2+). This latter observation is in sharp contrast to the releasing action of veratrine, which evoked release even in the absence of external Ca2+. Furthermore, the action of both C. noxius toxins was potentiated by veratrine, a result suggesting they have different mechanisms of action. Among drugs that release neurotransmitters by increasing Na+ permeability, it is noteworthy that scorpion toxins are the only ones yet reported to have a strict requirement for external Ca2+.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D051379:Mice; D009498:Neurotoxins / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014702:Veratrine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002121:Calcium Channel Blockers; C035413:Centruroides toxin; D007473:Ion Channels; D009498:Neurotoxins; D012604:Scorpion Venoms; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D014702:Veratrine; D002118:Calcium