The Chemistry of Poison Frogs

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The vibrant colours of poisonous frogs warn of the extremely toxic compounds contained in their skin. The amount of poison in one frog alone is estimated to be enough to kill 20,000 mice – but what are these compounds, where do they come from, and what makes the frogs immune to their effects? This graphic takes a look!

Poison dart frogs are native to the rainforests of Central and South America. There are over 170 different species, which come in a range of different bright colours; in fact, even within a single species there can be variations in colouration, which can lead to misidentification. Their vivid colours warn of their poisonous nature, but understanding these poisons has proved to be more of a challenge than you might expect.

To start with, scientists weren’t even sure where the poison was coming from. Initial theories were that the frogs were producing the poisons themselves, even though it was noted that the levels of toxic compounds in their skin decreased over time when they were kept in captivity. Studies which tried to prove that the frogs synthesised the compounds themselves failed, and this led scientists to consider another possibility: that the frogs were not creating the compounds themselves, but obtaining them from somewhere.

This led to the dietary hypothesis. Scientists noticed that frogs of the same species showed differences in the balance of poisonous compounds they contained over time, and wondered if this might be due to variations in their diets. Further investigation revealed the presence of specific poisonous alkaloid compounds which had only previously been known in ants and other arthropods, and it became clear that the frogs were somehow accumulating these compounds from their source of food into their skin. Exactly how they do this is an aspect of the story which is still unclear.

The poison that poison frogs contain is complex: over 800 different alkaloid compounds have been identified in the skin of various species. Many classes of these compounds have now had likely dietary sources identified, and different species of frog contain varying mixes of compounds. These can include pumiliotoxins, histrionicotoxins, gephyrotoxins, and many others. Perhaps the most well-known of these toxins, however, is batrachotoxin.

Batrachotoxin is one of the most toxic alkaloid poisons known. It’s found in a number of poisonous frogs, but at particularly high levels in three different species: the golden poison frog, the Kokoe poison frog, and the black-legged poison frog. The golden poison frog contains the highest levels of the compound, with a single frog estimated to contain enough batrachotoxin to kill 20,000 mice, or 10-20 adult humans. With such a high toxicity, you might wonder how the frog doesn’t just succumb to the poison itself when it obtains it from its diet?

Batrachotoxin kills due to its effect on sodium ion channels in the body. It binds to these channels and jams them open, interfering with nerve transmission and causing muscles to contract. Ultimately, this leads to heart palpitations, then cardiac arrest and death. Luckily for the frogs, they’re able to avoid this unpleasant fate, but until very recently scientists didn’t know exactly why. 

It turns out that the frogs avoid batrachotoxin’s effects thanks to a single mutation in their version of the sodium ion channel protein. This mutation doesn’t alter the properties of the sodium ion channel, but does confer resistance to batrachotoxin, meaning that the frogs are free to accumulate it without it killing them. As yet it’s still unclear how exactly the mutation makes it so much harder for batrachotoxin to bind to the channels, but further research may yet reveal the reasons.

Future research might also reveal a way of preventing batrachotoxin’s effect in humans, which would be welcome as there is currently no antidote to the compound. Apparently the closest thing we currently have to an antidote is, oddly enough, another poisonous compound: tetrodotoxin, the highly toxic chemical found in puffer fish. It works in the opposite way to batrachotoxin – it also binds to sodium ion channels, but jams them closed rather than open, so might temper batrachotoxin’s effects. It certainly doesn’t sound like the ideal treatment though, and I’ve been unable to find any record of it ever actually being used.

Finally, though they get less attention, there are plenty of other interesting stories amongst the other alkaloids found in poison frogs. One such example is epibatidine. This poisonous alkaloid binds to nicotinic acetylcholine receptors(nAChR) all over the body, causing convulsions, paralysis, and then death. Despite these toxic effects, it was also investigated as a potential painkiller, as binding to the receptors that it does gives it analgesic effects. However, as the dose at which pain is alleviated is also very close to the toxic dose, research into using it was discontinued.

 

 

 

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