Scientists have a new theory for why poisonous frogs do not poison themselves, which could ultimately lead to better antidotes for humans.
The golden poison frog, Phyllobates terribilis, is one of the world’s most poisonous animals. It owes this status to a nerve agent called batrachotoxin, which causes paralysis and cardiac arrest. Small molecules in the poison bind to special proteins in the cells of its victims, known as voltage-gated sodium channels.
These proteins govern the flow of electrical impulses in neurons, muscle and the heart.
A single golden poison frog, measuring about 5cm long, can carry a milligram of batrachotoxin in its skin glands, enough to kill between ten and twenty humans. Yet this little amphibian does not poison itself, even though it has its own voltage-gated sodium channels.
One explanation is that the frog has evolved sodium channels which resist the effects of its own poison. However, a new study appears to rule this out. Instead the researchers suggest that the frog carries a kind of antidote: yet another protein which mops up its poison molecules. If so, similar sponge-like proteins may ultimately make useful drugs to treat humans.
Advertisement
A team led by Professor Daniel Minor of the University of California, San Francisco, isolated sodium channel proteins from both the golden poison frog and from pitohui birds, which are also poisonous. They found in the laboratory that the channels were highly sensitive to the batrachotoxin poison. Indeed, those found in the frog reacted to the poison when only a tenth as much toxin was present as found in their wild cousins.
A previous study had reported that a genetic mutation observed in rats could make sodium channels immune to batrachotoxin, so Minor and his colleagues introduced this mutation into the pitohui and golden frog sodium channels.
This proved to be a dead end: the mutation failed to make the frog channels resistant to the poison. In fact it impaired the channels’ ability to function, even when the poison was not present.
Another experiment found that captive-raised poison frogs were resistant to the poison, even though their sodium channels, when isolated in the lab, were sensitive. Taken together, these observations suggest that the frogs rely on some other defence mechanism.
The researchers believe that the frogs produce sponge proteins that mop up the poison molecules and that this “toxin sequestration” keeps their sodium channels safe.
Advertisement
Minor suspects that the frogs use the sponge proteins to transport the poison, which is hundreds of times more toxic than cyanide, around their bodies. The frogs are thought to assimilate the toxins from insects that they eat.
“They have to move it from the gut to their skin,” he said. “They have to keep it safe till they can move it somewhere where it can be redeployed … We think these [sponge proteins] scoop up the toxin and then move it to somewhere that the animals can use it.”
The same idea could be used to create antidotes for nerve agents for which there are currently no cures, he believes, such as a poison produced by algae that causes so-called paralytic shellfish poisoning. “This could be a really important step in developing medicines for all kinds of disorders of the nervous system,” he said.
A similar system has been seen in bullfrogs. They produce a protein called saxiphilin, which can tightly bind to a related poison called saxitoxin and neutralise its harmful effects.
The researchers found that sodium channels from the golden poison frog were highly sensitive to saxitoxin, but not when saxiphilin was present.
Advertisement
“This demonstrates that high-affinity toxin-sponge proteins are able to prevent the actions of small molecule toxins that target sodium channels and lends support to the idea that toxin sequestration mechanisms may act to protect poisonous animals from autointoxication,” Dr Fayal Abderemane-Ali, a postdoctoral fellow who led the study, said.
Minor added: “Understanding these pathways may lead to the discovery of antidotes against various toxic agents.”
Scientists are unsure of the source of poison dart frogs’ toxicity; it is possible that they assimilate poisons from their insect prey. Poison dart frogs raised in captivity, away from the insects they eat in their natural habitat, do not develop poison.
The study has been published in the Journal of General Physiology.