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Differential effects of the recombinant toxin PnTx4(5-5) from the spider Phoneutria nigriventer on mammalian and insect sodium channels.
Paiva, Ana L B; Matavel, Alessandra; Peigneur, Steve; Cordeiro, Marta N; Tytgat, Jan; Diniz, Marcelo R V; de Lima, Maria Elena.
Afiliação
  • Paiva AL; Departamento de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
  • Matavel A; Departamento de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
  • Peigneur S; Toxicology and Pharmacology, KU Leuven, Leuven, Belgium.
  • Cordeiro MN; Departamento de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
  • Tytgat J; Toxicology and Pharmacology, KU Leuven, Leuven, Belgium.
  • Diniz MR; Departamento de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Belo Horizonte, Minas Gerais, Brazil.
  • de Lima ME; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: lima.mariaelena@gmail.com.
Biochimie ; 121: 326-35, 2016 Feb.
Article em En | MEDLINE | ID: mdl-26747232
The toxin PnTx4(5-5) from the spider Phoneutria nigriventer is extremely toxic/lethal to insects but has no macroscopic behavioral effects observed in mice after intracerebral injection. Nevertheless, it was demonstrated that it inhibits the N-methyl-d-aspartate (NMDA) - subtype of glutamate receptors of cultured rat hippocampal neurons. PnTx4(5-5) has 63% identity to PnTx4(6-1), another insecticidal toxin from P. nigriventer, which can slow down the sodium current inactivation in insect central nervous system, but has no effect on Nav1.2 and Nav1.4 rat sodium channels. Here, we have cloned and heterologous expressed the toxin PnTx4(5-5) in Escherichia coli. The recombinant toxin rPnTx4(5-5) was tested on the sodium channel NavBg from the cockroach Blatella germanica and on mammalian sodium channels Nav1.2-1.6, all expressed in Xenopus leavis oocytes. We showed that the toxin has different affinity and mode of action on insect and mammalian sodium channels. The most remarkable effect was on NavBg, where rPnTx4(5-5) strongly slowed down channel inactivation (EC50 = 212.5 nM), and at 1 µM caused an increase on current peak amplitude of 105.2 ± 3.1%. Interestingly, the toxin also inhibited sodium current on all the mammalian channels tested, with the higher current inhibition on Nav1.3 (38.43 ± 8.04%, IC50 = 1.5 µM). Analysis of activation curves on Nav1.3 and Nav1.5 showed that the toxin shifts channel activation to more depolarized potentials, which can explain the sodium current inhibition. Furthermore, the toxin also slightly slowed down sodium inactivation on Nav1.3 and Nav1.6 channels. As far as we know, this is the first araneomorph toxin described which can shift the sodium channel activation to more depolarized potentials and also slows down channel inactivation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Venenos de Aranha / Canais de Sódio / Escherichia coli / Neurotoxinas Limite: Animals Idioma: En Revista: Biochimie Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: França
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Venenos de Aranha / Canais de Sódio / Escherichia coli / Neurotoxinas Limite: Animals Idioma: En Revista: Biochimie Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Brasil País de publicação: França