Certain species of frogs in the genus Phyllobates have a powerful defensive adaptation−their skin can secrete a milky fluid that contains an extremely toxic compound called batrachotoxin (BTX). These frogs, which are found in Colombia, are known as poison dart frogs because some indigenous Colombian hunters coat the tips of their blowgun darts with the frogs' skin secretions. An animal hit by one of these darts dies quickly. What is the mechanism of action of BTX?

Batrachotoxin is one of the most potent biotoxins, more toxic than strychnine (250x approx.), causing ventricular fibrillation and neuromuscular toxicity. Its action mechanism is producing a conformational change that allows a permanent state of the channel opened that increases the resting sodium permeability. This generates action potentials in excitable membranes of nerve and muscle; causing the blocking of neuromuscular transmission and evoking muscular contracture. Death results from respiratory paralysis. In addition, BTX also causes arrhythmias, ventricular tachycardia, and fibrillation.

Explanation:

Batrachotixin (BTX, PubChem CID: 6324647), obtained from frogs of the genus Phyllobates of the Choco rain forest of Colombia, activate permanently the voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In addition, Li 2002 demonstrated an electrostatic ligand-receptor interaction at this site, possibly involving a charged tertiary amine on BTX.

- Cataldi, M. (2016). Batrachotoxin.

- Li, H. L., Hadid, D., & Ragsdale, D. S. (2002). The batrachotoxin receptor on the voltage-gated sodium channel is guarded by the channel activation gate. Molecular pharmacology, 61(4), 905-912.

- National Center for Biotechnology Information. PubChem Database. Batrachotoxin, CID=6324647, https://pubchem.ncbi.nlm.nih.gov/compound/Batrachotoxin (accessed on Dec. 4, 2019).