How Do Poison Frogs Resist Their Own Toxins?

Story at-a-glance -

  • Epibatidine is a poison frog toxin, which binds to receptors for the neurotransmitter acetylcholine, interfering with the nervous system
  • A DNA analysis of poison frogs that carry epibatidine revealed that their acetylcholine receptors were slightly misshapen, such that the toxin couldn’t recognize it but acetylcholine could
  • In the wild, poison dart frogs feast on certain ants and beetles that contain toxic steroidal alkaloid molecules, which is where most of their poison comes from; however, the exact source of epibatidine hasn’t been discovered

By Dr. Becker

Poison dart frogs carry powerful alkaloid toxins in their skin that are said to be 200 times more potent than morphine,1 quickly proving fatal to predators that dare to attack them. Yet, remarkably, the animals themselves are unaffected by the neurotoxins that easily kill others. Why? Researchers from the University of Texas at Austin looked into the poison frog toxin epibatidine, which binds to receptors for the neurotransmitter acetylcholine, interfering with the nervous system.

In order to carry epibatidine without being harmed, poison frogs would seemingly need to develop resistance to it in order to survive, but doing so would be difficult while still maintaining acetylcholine signaling, which, the researchers noted, “is essential for normal life.” In new research, they revealed the mechanism by which poison frogs are able to resist their own chemical defenses.2

Poison Frogs Have Slightly Misshapen Acetylcholine Receptors

A DNA analysis of poison frogs that carry epibatidine revealed that their acetylcholine receptors were slightly misshapen, such that the toxin couldn’t recognize it but acetylcholine could, National Geographic reported, “sparing the frogs the effects of their own toxic brew.”3 The study noted:4

“Studying the frog neurotoxin epibatidine, which binds to acetylcholine receptors, [researchers] found a single amino acid substitution. The substitution changes the configuration of the acetylcholine receptor, so that it decreases its sensitivity to the toxin.”

Such substitutions have occurred before, on three separate instances, the researchers reported, stating, “Expressing poison frog and human receptors in frog eggs revealed that different amino acid substitutions have occurred in different lineages that allow the frog to resist its own toxins while still letting target neurotransmitters function effectively.”5 Understanding this process may pave the way for scientists to harness epibatidine’s pain-relieving effects without the adverse side effects that typically go along with it.6

It’s one mystery unraveled in the case of poison frogs, but many more remain, like where epibatidine comes from in the frogs. In the wild, poison dart frogs feast on certain ants and beetles that contain toxic steroidal alkaloid molecules (which they either produce themselves or acquire via plants they eat), which is where most of the poison comes from.

However, the exact source of epibatidine hasn’t been discovered. The fact that epibatidine is shrouded in mystery isn’t unique in the world of frog poisons, however; of the 800 compounds known to exist in poison frogs, only about 70 are understood.7

Tadpoles Get Some Chemical Defenses From Their Moms

There are more than 100 species of poison dart frogs,8 at least one of which becomes poisonous while it’s still a tadpole. Strawberry poison frogs, which live in Central America and take on a bright red hue as adults, feed their tadpoles unfertilized eggs while they grow into frogs. It turns out those eggs contain low levels of alkaloid chemicals, courtesy of the mother, that is then transferred to the tadpoles, conferring some chemical defenses.9

What’s more, researchers found that the alkaloids worked to protect the tadpoles from predators, including bullet ants, which were nine times more likely to attack nontoxic tadpoles than poisonous ones.10

At any rate, since the poisons are not produced in the frogs, but rather come from their diet (and in some species, their mother) and is then secreted from their skin, poison frogs raised in captivity tend to lose their poison because they feast on nonalkaloid fruit flies, mealworms, crickets and termites — eventually becoming harmless.

The Brighter the Frog, the More Poisonous It Is

In case you were wondering, wild poison dart frogs got their name because native tribes would routinely dip the tips of their arrows in the frog poison, rendering them lethal, reportedly for up to a year.11 It was easy to pick out which frogs harnessed deadly poison, because they boast vivid colors ranging from yellow and green to blue and red. In nature, the frogs’ bright colors signal would-be predators to stay away, and while sometimes this is a bluff, in the cause of frogs, color matters.

When researchers asked human observers to rank different poison frog species based on contrast of colors, and also used a computer program to measure color contrast, it turned out that brighter frogs were also more toxic.12 Again, since it’s the frogs’ diet that lends them their poison, it makes sense that dietary changes would influence their chemical punch, and there is some research that frogs living in pristine forests have a greater diversity of alkaloids in their skin compared to those living in a disturbed habitat.13

The reduction in alkaloid variety is likely due to a reduction in arthropod species (insects) in the frogs' diets and could be a sign that, if poison frogs continue to lose habitat due to the destruction of rainforests, their numbers may not only decrease but along with them, their poison.