Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on “toxin sponge” proteins

Many poisonous organisms carry small-molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui poison birds and Phyllobates frogs stands out because of its lethality unusual effects on NaV How these toxin-bearing avoid autointoxication remains poorly understood. In frogs, a DIVS6 pore-forming helix N-to-T mutation has been proposed as the BTX resistance mechanism. Here, we show this variant is absent frog NaVs, incurs strong cost compromising function, fails to produce BTX-resistant channels in NaVs.