Peptide toxins that target vertebrate voltage-gated sodium channels underly the painful stings of harvester ants

Samuel D Robinson; Jennifer R Deuis; Pancong Niu; Axel Touchard; Alexander Mueller; Vanessa Schendel; Nina Brinkwirth; Glenn F King; Irina Vetter; Justin O Schmidt

doi:10.1016/j.jbc.2023.105577

Peptide toxins that target vertebrate voltage-gated sodium channels underly the painful stings of harvester ants

J Biol Chem. 2024 Jan;300(1):105577. doi: 10.1016/j.jbc.2023.105577. Epub 2023 Dec 16.

Authors

Affiliations

¹ Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia. Electronic address: sam.robinson@uq.edu.au.
² Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia.
³ CNRS, UMR Ecologie des forêts de Guyane - EcoFoG (AgroParisTech, CIRAD, INRAE, Université de Guyane, Université des Antilles), Kourou, France.
⁴ Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia; Centro de Investigación Biomédica CENBIO, Universidad UTE, Quito, Ecuador.
⁵ Nanion Technologies, Munich, Germany.
⁶ Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia; Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Queensland, Brisbane, Queensland, Australia.
⁷ Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia; School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
⁸ Southwestern Biological Institute, Tucson, Arizona, USA.

Abstract

Harvester ants (genus Pogonomyrmex) are renowned for their stings which cause intense, long-lasting pain, and other neurotoxic symptoms in vertebrates. Here, we show that harvester ant venoms are relatively simple and composed largely of peptide toxins. One class of peptides is primarily responsible for the long-lasting local pain of envenomation via activation of peripheral sensory neurons. These hydrophobic, cysteine-free peptides potently modulate mammalian voltage-gated sodium (Na_V) channels, reducing the voltage threshold for activation and inhibiting channel inactivation. These toxins appear to have evolved specifically to deter vertebrates.

Keywords: Pogonomyrmex; ion channel; neuron; pain; venom.

MeSH terms

Animals
Ants* / pathogenicity
Ants* / physiology
Bites and Stings* / complications
Pain* / chemically induced
Pain* / complications
Peptides* / chemistry
Peptides* / pharmacology
Peptides* / toxicity
Sensory Receptor Cells / drug effects
Sensory Receptor Cells / physiology
Toxins, Biological* / chemistry
Toxins, Biological* / pharmacology
Toxins, Biological* / toxicity
Vertebrates
Voltage-Gated Sodium Channel Blockers* / chemistry
Voltage-Gated Sodium Channel Blockers* / pharmacology
Voltage-Gated Sodium Channel Blockers* / toxicity
Voltage-Gated Sodium Channels* / metabolism

Substances

Peptides
Toxins, Biological
Voltage-Gated Sodium Channel Blockers
Voltage-Gated Sodium Channels