title: Bothriurus bonariensis scorpion venom activates voltage-dependent sodium channels in insect and mammalian nervous systems.
abstract: Animal venoms have been widely recognized as a major source of biologically active molecules. Bothriurus bonariensis, popularly known as black scorpion, is the arthropod responsible for the highest number of accidents involving scorpion sting in Southern Brazil. Here we reported the first attempt to investigate the neurobiology of B. bonariensis venom (BBV) in the insect and mammalian nervous system. BBV (32 μg/g) induced a slow neuromuscular blockade in the in vivo cockroach nerve-muscle preparations (70 ± 4%, n = 6, p < 0.001), provoking repetitive twitches and significantly decreasing the frequency of spontaneous leg action potentials (SNCAPs) from 82 ± 3 min(-1) to 36 ± 1.3 min(-1) (n = 6, p < 0.05), without affecting the amplitude. When tested in primary cultures of rat hippocampal cells, BBV induced a massive increase of Ca(2+) influx (250 ± 1% peak increase, n = 3, p < 0.0001). The disturbance of calcium homeostasis induced by BBV on the mammalian central nervous system was not accompanied by cellular death and was prevented by the co-treatment of the hippocampal cells with tetrodotoxin, a selective sodium channel blocker. The results suggest that the biological activity of BBV is mostly related to a modulation of sodium channels function. Our biological activity survey suggests that BBV may have a promising insecticidal and therapeutic potential.
authors.affiliation: LPA, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil; LANETOX, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, (PPGBTox), Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, 97105-900, Santa Maria, RS, Brazil.
authors.forename: Douglas Silva
authors.initials: DS
authors.lastname: Dos Santos
authors.affiliation: LPA, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil.
authors.forename: Evelise Leis
authors.initials: EL
authors.lastname: Carvalho
authors.affiliation: LPA, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil.
authors.forename: Jeferson Camargo
authors.initials: JC
authors.lastname: de Lima
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Ricardo Vaz
authors.initials: RV
authors.lastname: Breda
authors.affiliation: LANETOX, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil.
authors.forename: Raquel Soares
authors.initials: RS
authors.lastname: Oliveira
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular (PPGBCM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9500, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Thiago Carrazoni
authors.initials: TC
authors.lastname: de Freitas
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Simone Denise
authors.initials: SD
authors.lastname: Salamoni
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular (PPGBCM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9500, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Michelle Flores
authors.initials: MF
authors.lastname: Domingues
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular (PPGBCM), Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9500, 91501-970, Porto Alegre, RS, Brazil.
authors.forename: Angela Regina
authors.initials: AR
authors.lastname: Piovesan
authors.affiliation: LPA, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil.
authors.forename: Juliano Tomazzoni
authors.initials: JT
authors.lastname: Boldo
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Dênis Reis
authors.initials: DR
authors.lastname: de Assis
authors.affiliation: Instituto do Cérebro (INSCER), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil.
authors.forename: Jaderson Costa
authors.initials: JC
authors.lastname: da Costa
authors.affiliation: LANETOX, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil; Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, (PPGBTox), Universidade Federal de Santa Maria (UFSM), Av. Roraima 1000, 97105-900, Santa Maria, RS, Brazil. Electronic address: charistonbelo@unipampa.edu.br.
authors.forename: Cháriston André
authors.initials: CA
authors.lastname: Dal Belo
authors.affiliation: LPA, Universidade Federal do Pampa (UNIPAMPA), Av. Antônio Trilha 1847, 97300-000, São Gabriel, RS, Brazil.
authors.forename: Paulo Marcos
authors.initials: PM
authors.lastname: Pinto
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003058:Cockroaches / Q000378:metabolism*; D005121:Extremities / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000473:pathology; D015640:Ion Channel Gating / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008322:Mammals / Q000378:metabolism*; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology*; D012605:Scorpions / Q000737:chemistry*; D015222:Sodium Channels / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D012604:Scorpion Venoms; D015222:Sodium Channels; D013779:Tetrodotoxin; D002118:Calcium
keywords: Arthropods; Calcium influx; Neuromuscular blockade; Neurotoxicity; Poison