Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Food Science & Technology, Toxicology, Phoneutria nigriventer, voltage-gated sodium channel, spider, insecticide, peptide toxin PnTx2-1, gating modifier toxin, AMINO-ACID-SEQUENCE, MISSULENA-BRADLEYI, LETHAL NEUROTOXIN, ERECTILE FUNCTION, VENOM PEPTIDES, WEB, PURIFICATION, DISCOVERY, KINETICS, KEYS, Animals, Female, Insecta, Ion Channel Gating, Male, Neuropeptides, Neurotoxins, Oocytes, Protein Isoforms, Sodium Channels, Spider Venoms, Spiders, Xenopus laevis, 0601 Biochemistry and Cell Biology, 1115 Pharmacology and Pharmaceutical Sciences, 3214 Pharmacology and pharmaceutical sciences

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.