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

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2018 Aug 24

PMID 30134593

Citations 4

Authors

Steve Peigneur

Ana Luiza B Paiva

Marta N Cordeiro

Marcia H Borges

Marcelo R V Diniz

Maria Elena De Lima

Jan Tytgat

Affiliations

Soon will be listed here.

Abstract

Spider venoms are complex mixtures of biologically active components with potentially interesting applications for drug discovery or for agricultural purposes. The spider 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-channel isoforms, one insect Na channel and one arachnid Na channel. Furthermore, comparison of the activity of both PnTx2-1 and PnTx2-6 on Na1.5 channels reveals that this family of toxins modulates the cardiac Na 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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