How poison dart frogs avoid poisoning themselves

Scientists have wondered how golden poison dart frogs resist succumbing to the high doses of toxin they store in their skin. Certain species of Phyllobates frogs are loaded with enough batrachotoxin—up to 2 mg in adults—to kill more than 20,000 mice, yet their voltage-gated sodium channel membrane protein is immune to its paralytic effects. Sho-Ya Wang and Ging Kuo Wang of the University at Albany now report that a single amino acid swap can render sodium channels almost completely resistant to batrachotoxin. The researchers built off a study published last year by another research team that identified five amino acid substitutions differentiating poison dart frog and rat sodium channels. In the new study, scientists tested whether creating the five frog substitutions in the rat sodium channel, individually and in combination, conferred batrachotoxin resistance. Monitoring cells engineered to produce either normal or modified sodium channels revealed that replacing just one amino acid—asparagine with threonine at position 1,584—conferred “exceptional” batrachotoxin resistance (Proc. Natl. Acad. Sci. USA 2017, DOI: 10.1073/pnas.1707873114). Sodium channels with substitutions at the other four locations remained sensitive to the toxin. Sho-Ya Wang says gaining a better understanding of how batrachotoxin interacts with sodium channels may help improve the design of therapeutic drugs that target the same region of the protein.