The most poisonous animal in the world is difficult to quantify, but one of the most deadly is, without question, the golden poison frog (Phyllobates terribilis), native to Colombia. But how does it avoid killing itself with its toxins?
They look adorable, but within their skin glands, they store an alkaloid toxin called batrachotoxin. Enough of it, on average, to kill 10 human beings — if the poison enters your bloodstream, you'll likely be dead in under 10 minutes.
There's only one known species that is resistant to it (a snake), and there is no known antidote.
The frogs don't create the toxin themselves. When removed from their natural environment and bred in captivity, they are completely harmless, which has led to the accepted theory that, like poisonous puffer fish, the frogs synthesise the toxin from their diet.
So why don't they die of it themselves? To figure it out, researchers from the State University of New York (SUNY) turned to rats.
Batrachotoxin works by irreversibly opening the sodium channels of nerve cells, which permanently blocks the transmission of nerve signals to the muscles, while preventing the muscles from being able to relax. The heart is particularly susceptible, and the end result is cardiac failure.
Puffer fish tetrodotoxin also works on the sodium channel, although the mechanism is slightly different. But they have a single amino acid mutation that modifies their sodium channels so that they are immune to their own poison.
The researchers, Sho-Ya Wang and Ging Kuo Wang, looked to amino acids for the frogs' immunity.
Using rat muscle, they tested five naturally occurring amino acid substitutions that had been found within P. terribilis muscle. When all five of the rat amino acids were replaced with the frog mutations, the rat muscle was completely resistant to batrachotoxin.
The next step was to try the substitutions one by one. All but one still showed a high sensitivity to the toxin. The one substitution that remained resistant is called N1584T. For this mutation, the amino acid asparagine is replaced with the amino acid threonine.
Previous research conducted by a Harvard team suggested there were multiple origins for the frogs' resistance to their own toxin, but the SUNY team's research suggests that, like the puffer fish, the frogs' resistance comes mainly from a single genetic mutation.
This doesn't mean we'll be able to find an antidote, though. There is still no known antidote for puffer fish toxin. The purpose of the study was to find the mutation that makes the endangered frogs immune to their own toxin.
"Our results strongly support the conclusion that batrachotoxin autoresistance in P. terribilis muscle sodium channels is primarily due to an equivalent rNav1.4- N1584T substitution, which eliminates nearly all batrachotoxin actions," the study's conclusion reads.
"Whether a reverse mutant remains partially batrachotoxin-resistant as predicted by stepwise increases of toxin autoresistance in poison frogs during evolution merits additional studies."
The research has been published in the journal PNAS.