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.
Highlights
Spiders can be considered one of the most successful venomous animals ever to inhabit the planet with over 47,000 species characterized to date [1]
PnTx2-6 arewhich the best-characterized from the Phoneutria nigriventer venom fraction
The characterization of PnTx2-1 as a NaV -channel modulator adds to the expanding knowledge on the Phoneutria nigriventer venom
Summary
Spiders can be considered one of the most successful venomous animals ever to inhabit the planet with over 47,000 species characterized to date [1]. Despite this diversity, no more than 100 spider species. Spiders can be considered one of the most successful venomous animals ever to inhabit ofthe planet with over 47,000 species characterized to date [1]. Despite this diversity, no more than 100 spider species have had their venom investigated [2]. Phoneutria nigriventer are very in drug andsolitary bioinsecticide [1,5,6].
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