Single rat muscle Na+ channel mutation confers batrachotoxin autoresistance found in poison-dart frog Phyllobates terribilis

Phyllobates terribilis frog is listed as an endangered species, endemic to the Pacific coast of Colombia. Through diets, these golden poison frogs sequester lethal amounts of batrachotoxin in their skin for self-defense. Batrachotoxin activates voltage-gated Na⁺ channels and keeps them open persistently with deadly consequences. This study addresses how golden poison frogs may avoid poisoning themselves via a naturally occurring substitution at the batrachotoxin receptor within their muscle Na⁺ channel. An equivalent asparagine-to-threonine substitution not only preserved the functional integrity of rat muscle Na⁺ channels but also rendered them exceptionally resistant to batrachotoxin. Such a switch could evolve via a single nucleotide mutation.