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

Harvester ants (genus Pogonomyrmex) are notable 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. These hydrophobic, cysteine-free peptides activate mammalian sensory neurons via potent modulation of voltage-gated sodium (NaV) channels, reducing voltage threshold for activation and inhibiting channel inactivation. These toxins appear to have evolved specifically as deterrents against vertebrates.