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Toxins 2018, 10(9), 337; https://doi.org/10.3390/toxins10090337

Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating

1
Toxicology and Pharmacology, University of Leuven (KU Leuven), Campus Gasthuisberg, P.O. Box 922, Herestraat 49, 3000 Leuven, Belgium
2
Laboratório de Venenos e Toxinas Animais, Dept de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil
3
Departamento de Pesquisa e Desenvolvimento, Fundação Ezequiel Dias, Minas Gerais, Belo Horizonte 30510-010, Brazil
4
Programa de Pós-graduação em Ciências da Saúde, Biomedicina e Medicina, Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte, Grupo Santa Casa de Belo Horizonte, Minas Gerais, Belo Horizonte 31270-901, Brazil
These two authors contribute equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 26 July 2018 / Revised: 15 August 2018 / Accepted: 16 August 2018 / Published: 21 August 2018
(This article belongs to the Section Animal Venoms)
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Abstract

Spider venoms are complex mixtures of biologically active components with potentially interesting applications for drug discovery or for agricultural purposes. The spider Phoneutria nigriventer is responsible for a number of envenomations with sometimes severe clinical manifestations in humans. A more efficient treatment requires a comprehensive knowledge of the venom composition and of the action mechanism of the constituting components. PnTx2-1 (also called δ-ctenitoxin-Pn1a) is a 53-amino-acid-residue peptide isolated from the venom fraction PhTx2. Although PnTx2-1 is classified as a neurotoxin, its molecular target has remained unknown. This study describes the electrophysiological characterization of PnTx2-1 as a modulator of voltage-gated sodium channels. PnTx2-1 is investigated for its activity on seven mammalian NaV-channel isoforms, one insect NaV channel and one arachnid NaV channel. Furthermore, comparison of the activity of both PnTx2-1 and PnTx2-6 on NaV1.5 channels reveals that this family of Phoneutria toxins modulates the cardiac NaV channel in a bifunctional manner, resulting in an alteration of the inactivation process and a reduction of the sodium peak current. View Full-Text
Keywords: Phoneutria nigriventer; voltage-gated sodium channel; spider; insecticide; peptide toxin PnTx2-1; gating modifier toxin Phoneutria nigriventer; voltage-gated sodium channel; spider; insecticide; peptide toxin PnTx2-1; gating modifier toxin
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Peigneur, S.; Paiva, A.L.B.; Cordeiro, M.N.; Borges, M.H.; Diniz, M.R.V.; de Lima, M.E.; Tytgat, J. Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating. Toxins 2018, 10, 337.

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