Why don't poison dart frogs poison themselves?

07 September 2017
Posted by Chris Smith.

Lacing your skin with a chemical cocktail capable of killing 20,000 mice sounds like suicide, but Central and South American poison dart frogs are powerfully immune to their own poison, and now scientists know why.

For thousands of years, indigenous tribes like the Noanamá Chocó and Emberá Chocó in Columbia, have smeared the sharp tips of their blow darts and arrows with secretions from poison dart frog's skin.

These secretions contain chemicals called batrachotoxins, which the animals pick up from the centipedes and other insects that form part of their rainforest diet. The frogs concentrate the toxins in glands under their skin, where, together with brightly coloured markings and other bitter-tasting molecules, they're intended to serve as a deterrent to predators looking for a frog-sized meal.

For any animal cavalier enough to try anyway, death comes swiftly, by paralysis. The toxin binds to electrical channels, called voltage-gated sodium conductances, or VOCs, which are present in the membranes of muscle cells. These channels excite the cell in response to nerve signals, making the muscle contract, but they need to remain open for only a fraction of a second to achieve this effect. 

Batrachotoxin throws a spanner in these works by jamming open the conductance, flooding the cell with sodium and rendering it unresponsive. The potency of the chemical is incredible: just one hundred millionths of a gram, the equivalent of a couple of grains of table salt, is sufficient to kill an adult human.

So why, despite packing this kind of chemical firepower within their own bodies, are these frogs unaffected by their own poison?

Writing in PNAS, State University of New York duo Sho-Ya Wang and Ging Juo Wang, have solved the mystery. Both frogs and other larger animals, like us, have sodium channels of the type targeted by batrachotoxin. But when scientists compared the DNA code containing the instructions for making the sodium channels, the frogs genetic sequence contained five changes compared with the DNA code found in a rat or mouse. Did these differences account for the frogs resistance to its own chemical arsenal?

To find out, the New York duo engineered the same genetic changes found in the frogs into cultured humans cells, called HEK293t cells, and tested their sensitivity to batrachotoxin exposure. One of the five genetic changes, a switch of a single amino acid building block in the protein that forms the sodium channel, rendered the cells completely insensitive to the toxin.

This change can be achieved by swapping a single genetic DNA letter A for a letter C. So it's tempting to speculate that the frogs have naturally evolved this simple change which has enabled them to acquire, accumlate and then re-deploy these toxins from their diet and use them for defence. 

Aside from making a neat evolutionary and biochemical story, discoveries like this matter because they provide new insights into how nerves and muscle cells operate, and highlight novel targets for the development of drugs and other therapeutics.

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