How it works

Tetrodotoxin is known to selectively block off the voltage-sensitive Na⁺-channels of excitable tissues and neuronal transmission in skeletal muscles. These channels are critical for cellular signaling pathways (e.g. transmission of impulses and the mediation of many cell functions). When a neuron (nerve cell) sends a message, tiny pores or channels in the neuron's membrane open up to let sodium ions enter the cell. Tetrodotoxin can block these tiny pores, which in turn prevents any signaling in the nervous system.

The guanidinium ion is able to enter cells by mimicking the hydrated sodium cation. It is likely that the imidazole ring is the part of the molecule that lodges in the channel leaving the rest of the molecule blocking its outer mouth. The danger comes from the tenacity of the TTX molecule. This is clearly demonstrated by the comparison between the occupancy times of TTX and the hydrated sodium ion. Hydrated sodium reversibly binds on a nanosecond time-scale, whereas TTX binds and remains on the order of tens of seconds. With the bulk of the TTX molecule denying sodium the opportunity to enter the channel, sodium movement is effectively shut down, and the action potential along the nerve membrane ceases. The result is rapid paralysis and possibly death.