ACMT Toxicology Visual Pearl: Poison Dart Frog

3. Grayanotoxin – a sodium channel opener

Background

The golden poison dart frog (Phyllobates terribilis), often considered one of the most poisonous animals on the planet, secretes onto its skin the lipophilic alkaloid batrachotoxin, which irreversibly activates voltage-gated sodium channels, like grayanotoxin which can be found in rhododendron [1, 2].

Poison dart frogs are found in the rainforest regions of Central and South America and derive their name from the Choco people who used the poison to coat the tips of their blow darts. Because the toxin can be absorbed cutaneously, the natives used waxy leaves as gloves during the preparation of extracting the secretions from glands on the skin [3]. The amount of toxin collected from one frog is potent enough to kill 10 humans and can be used to cover 30-50 darts for hunting [4]. The LD₅₀, or dose to kill half of mice in studies, of batrachotoxin is 2-3 μg/kg subcutaneously [5]. For comparison, the LD₅₀ for the sodium channel blocker tetrodotoxin that is found in pufferfish (fugu) is 12.5–16 µg/kg [6, 7], and the LD₅₀ for the feared box jellyfish is 40 μg/kg [8], highlighting the significant toxicity of batrachotoxin and placing it amongst the most poisonous animals on the planet. While the golden poison dart frog is one of the most potent in terms of toxicity, there are over 200 species of poisonous frogs in the Dendrobatidae family [9]. Recently, identical toxins have been identified in several species of birds in New Guinea [10].

Interesting facts about the poison dart frog and its toxin

• Poison dart frogs do not synthesize the alkaloid toxins, such as batrachotoxin, but rather concentrate them from their diet, which consists mainly of small wild insects such as ants, termites, centipedes, beetles [3]. When raised in captivity (e.g., zoos), they are often not poisonous due to the altered diet [11].
• Poison dart frogs have mutated sodium channels and thus have developed resistance to their own batrachotoxin [12].
• The combination of bright coloration along with a potent neurotoxin is termed aposematism and is useful in warding off predators [13].
• Because toxin can be absorbed through the skin, humans can become poisoned by handling the animal without gloves.

How does poison dart frog toxicity present? Is there any treatment?

• Batrachotoxin irreversibly binds voltage-gated sodium channels, causing irreversible depolarization of nerves and muscles, ultimately causing paralysis, dysrhythmia, and cardiac arrest [1,2].
• Management is supportive care and there is no effective antidote.
• Sodium channel blockers such as lidocaine and tetrodotoxin have been proposed as competitive antagonists and noncompetitive inhibitors, respectively [14].

Clinical Pearls

• Poison dart frogs are among the most poisonous animals on the planet, although when raised in captivity are often nonpoisonous.
• They contain batrachotoxin which irreversibly modulates voltage-gated sodium channels causing irreversible depolarization and ultimately paralysis, arrhythmia, and cardiac arrest.
• Treatment is supportive.