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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
Author(s) -
Sitges María,
Possani Lourival Domingos,
Bayón Alejandro
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05732.x
Subject(s) - venom , synaptosome , sodium channel , toxin , biology , chemistry , biophysics , pharmacology , biochemistry , sodium , membrane , organic chemistry
Toxic peptides II‐9.2.2 and II‐10, purified from Centruroides noxius venom, bear highly homologous N‐ter‐minal 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 γ‐[ 3 H]aminobutyric acid ([ 3 H]GABA). Their effect was completely blocked by tetro‐dotoxin 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 Ca 2+ and was blocked by Ca 2+ channel blockers (verapamil and Co 2+ ). This latter observation is in sharp contrast to the releasing action of veratrine, which evoked release even in the absence of external Ca 2+ . 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 neuro‐transmitters by increasing Na + permeability, it is noteworthy that scorpion toxins are the only ones yet reported to have a strict requirement for external Ca 2+ .