Intrahippocampal injection of TsTX-I, a beta-scorpion toxin, causes alterations in electroencephalographic recording and behavior in rats.
OBJECTIVE
TsTX-I scorpion toxin, also known as γ-toxin, is a β-toxin which binds to site 4 of the sodium channel, shifting its activation potential. There are few studies about its pharmacological action in the central nervous system. The objective of this work was to determine the electroencephalographic, behavioral and histopathological effects of intrahippocampal injection of TsTX-I.


METHODS
Rats were anesthetized and fitted with cannulae for injection into the hippocampus and with electrodes for cerebral recording. The animals were treated with Ringer solution, some doses of TsTX-I, DMSO 0.1% or veratridine. Behavioral and electrographic recordings were observed for 4 hours after the injection. After 7 days, the rats were perfused, and their brains removed for histological analysis.


RESULTS
Increasing doses of the toxin evoked epileptic-like discharges, wet dog shakes, and in some cases hind limb paralysis and intense respiratory difficulty followed by death. The histopathological analysis demonstrated no cell loss. Animals injected with veratridine developed epileptiform activity in the electrographic recording and neuronal loss.


CONCLUSIONS
The results suggest that TsTX-I toxin may be responsible, at least in part, for the epileptic and behavioral effects observed with the crude venom, and although veratridine and TsTX-I act on Na-channel, the differences between them are remarkable, demonstrating that toxins can have different functional effects depending on the site of action in the channel. Thus, animal neurotoxins are often highly selective and may be useful for the identification of the sequence of events underlying neurotransmission.
Teixeira
Vanessa Fernanda
VF
Laboratory of Pharmacology, Butantan Institute, 05503-900 São Paulo, SP, Brazil.
Conceição
Isaltino Marcelo
IM
Lebrun
Ivo
I
Nencioni
Ana Leonor A
AL
Coronado Dorce
Valquiria A
VA
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006614:Hindlimb; D006624:Hippocampus / Q000378:metabolism*; D007267:Injections; D008297:Male; D010243:Paralysis / Q000139:chemically induced; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000633:toxicity*
D012604:Scorpion Venoms; D015222:Sodium Channels; C482042:TsTX-I, mouse; D014701:Veratridine