TSII toxin isolated from Tityus serrulatus scorpion venom: behavioral, electroencephalographic, and histopathologic studies.
We have reported earlier that intrahippocampal administration of the C-pool from Tityus serrulatus scorpion venom induces convulsions in rats. Here we report the effects of seven toxins isolated from the C-pool. The strongest effects were seen after toxin 5C, which was sequenced and identified as TSII, a beta-type toxin that affects Na+ channel activation. Unilateral injection of TSII in the rat hippocampus (1.7 microg/microl) induced clusters of spikes and epileptic discharges of mainly moderate intensity, convulsion-related behavioral changes (wet dog shakes, staring, masticatory jaw movements, facial automatisms, orofacial movements, intense sniffing, blinking, and forelimb clonus with rearing and falling) and a massive neuronal loss of pyramidal cells in the ipsilateral CA1, CA3, and CA4 subfields and of granulate cells of the ipsilateral dentate gyrus. Toxins C3, C4, and C6 induced weaker changes in the EEG and behavioral changes and failed to induce cell death, and toxins C1, C2, and C7 had no effects. The similarities in the effects of TsTx, a alpha-type toxin that affects Na+ channel, suggest that the loss of modulation of activation of the sodium channel caused by TSII increases glutamate release, leading to long-lasting increases in intracellular Ca2+ and cell death.
Sandoval
Maria Regina Lopes
MR
Laboratory of Pharmacology, Butantan Institute, São Paulo, SP 05503 900, Brazil. mrlsando@usp.br
Lebrun
Ivo
I
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004569:Electroencephalography / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000008:administration & dosage / Q000302:isolation & purification* / Q000633:toxicity*; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry* / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced
D009498:Neurotoxins; D012604:Scorpion Venoms