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

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 mo...

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Autores principales: Peigneur, Steve, Paiva, Ana Luiza B., Cordeiro, Marta N., Borges, Márcia H., Diniz, Marcelo R. V., de Lima, Maria Elena, Tytgat, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162791/
https://www.ncbi.nlm.nih.gov/pubmed/30134593
http://dx.doi.org/10.3390/toxins10090337
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author Peigneur, Steve
Paiva, Ana Luiza B.
Cordeiro, Marta N.
Borges, Márcia H.
Diniz, Marcelo R. V.
de Lima, Maria Elena
Tytgat, Jan
author_facet Peigneur, Steve
Paiva, Ana Luiza B.
Cordeiro, Marta N.
Borges, Márcia H.
Diniz, Marcelo R. V.
de Lima, Maria Elena
Tytgat, Jan
author_sort Peigneur, Steve
collection PubMed
description 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 Na(V)-channel isoforms, one insect Na(V) channel and one arachnid Na(V) channel. Furthermore, comparison of the activity of both PnTx2-1 and PnTx2-6 on Na(V)1.5 channels reveals that this family of Phoneutria toxins modulates the cardiac Na(V) channel in a bifunctional manner, resulting in an alteration of the inactivation process and a reduction of the sodium peak current.
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spelling pubmed-61627912018-10-03 Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating Peigneur, Steve Paiva, Ana Luiza B. Cordeiro, Marta N. Borges, Márcia H. Diniz, Marcelo R. V. de Lima, Maria Elena Tytgat, Jan Toxins (Basel) Article 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 Na(V)-channel isoforms, one insect Na(V) channel and one arachnid Na(V) channel. Furthermore, comparison of the activity of both PnTx2-1 and PnTx2-6 on Na(V)1.5 channels reveals that this family of Phoneutria toxins modulates the cardiac Na(V) channel in a bifunctional manner, resulting in an alteration of the inactivation process and a reduction of the sodium peak current. MDPI 2018-08-21 /pmc/articles/PMC6162791/ /pubmed/30134593 http://dx.doi.org/10.3390/toxins10090337 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Peigneur, Steve
Paiva, Ana Luiza B.
Cordeiro, Marta N.
Borges, Márcia H.
Diniz, Marcelo R. V.
de Lima, Maria Elena
Tytgat, Jan
Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating
title Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating
title_full Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating
title_fullStr Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating
title_full_unstemmed Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating
title_short Phoneutria nigriventer Spider Toxin PnTx2-1 (δ-Ctenitoxin-Pn1a) Is a Modulator of Sodium Channel Gating
title_sort phoneutria nigriventer spider toxin pntx2-1 (δ-ctenitoxin-pn1a) is a modulator of sodium channel gating
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162791/
https://www.ncbi.nlm.nih.gov/pubmed/30134593
http://dx.doi.org/10.3390/toxins10090337
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