On 24th of June, Amber Ahark (Y11), who has written an article about poisonous frogs during the COVID-19 lockdown, did a virtual Café Sci talk about her research. She told us how poison frogs are able to hold a neurotoxin within their skin, called batrachotoxin (BTX), which is capable of killing 20,000 mice or the equivalent of 10 grown men. A rare breed of frog called Phyllobates terribilis which originates from Colombia and are bright yellow in colour. Their sizes vary from 1.5 to 6cm. These poisonous frogs secrete the venom from their skin, as the BTX toxin is stored in glands beneath their skin; they absorb the toxins and chemicals from prey such as mice and ants. Once the toxin is injected into an animal, then the toxin disrupts the nervous system by tearing open sodium channels and interferes with the body’s ability to transmit electrical signals. This then leads to hypertension, fibrillation, heart failure or in more severe cases, a seizure. The toxin BTX belongs to the alkaloid group[1] and this was isolated from the bodies of the frogs in Colombia to shoot poison at enemies using blow darts. It is argued that BTX could be used in the future to formulate pain killers, as it has been synthesized and reproduced in laboratories using cis-decalone. The structure of BTX includes a steroid skeleton and an oxazapane ring and the activity of BTX depends on temperature, reaching its maximum at 37 degrees Celsius. However, poisonous frogs are not the only creatures to contain traces of BTX. It was found that Choresine beetles also had high concentrations of the neurotoxin and this leads to speculation that these beetles could be a staple part of the frogs’ diets, as they sequester the toxin from their prey. Essentially, BTX poisons the body by interfering with nerve signals. Within our cells, we have a high concentration of sodium ions outside our cells while the potassium ions are more concentrated within our cells. The movement of these ions are controlled by channels (sodium and potassium channels), and the sodium channels are closed. However, when BTX enters the body, it rapidly opens these sodium channels and it binds to the threshold voltage. BTX inhibits nerve impulses, by binding to the gates of the sodium channels and it becomes irreversible- so the sodium channels cannot be closed. Ultimately, this suggests that the survival rate against BTX is incredibly slim. However, how do poisonous frogs manage to store the neurotoxin within their bodies?
A 2014 study from John Carroll University discovered that the mother frogs give the tadpoles poison, which they absorb to become poisonous themselves. As tadpoles, their mother feeds them her own unfertilised eggs, which contain BTX. Although, these poisonous dart frogs were never poisonous, they evolved to become poisonous and store toxins because of a mutation. This was a very small mutation, where three of the 2,500 amino acids in a receptor changed. This mutation prevented BTX from damaging their own receptors and destroying their nervous system, making them resistant. The mutation that makes the frogs resistance to the toxin occurs in the parts of the receptor that are close to but don't touch the toxin (epibatidine). The amino acids are never in contact with the neurotoxin, yet they can still change the receptor. The receptor's key function was maintained by additional amino acid replacements allowing them to resist their own toxins, while still maintaining the normal function of their target neurotransmitters. Furthermore, some poison frogs managed to retune a neurotransmitter receptor so that it also became insensitive to another toxin, called epibatidine. Overall, despite these poisonous frogs being lethal and capable of killing humans due to the neurotoxin BTZ, they don’t produce it themselves, but sequester the toxin from feeding off their mother’s unfertilised embryos and their prey. Additionally, due to a mutation, their receptors are resistant to the toxin because of a change in their amino acid sequence within their receptors.
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June 2020
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