- How it Works -

Click here to review concepts of Ion Channels and Action Potential

- Tetrodotoxin (TTX) binds specifically to sodium channels by mimicking the hydrated Na+ ion,
denying entry to Na+ ions. It is considered as an irreversible inhibitor.

- The diagram below shows the sodium channel with 4 repeating units. The TTX bind site is
represented by the orange filled circles on the connecting segments between S5 and S6.


" Sodium channel and TTX binding sites"

- The TTX-Na channel binding site is extremely tight (Kd = 10-10 nM)

- It has been proposed that the binding between TTX and the Na channel results from the interaction
between the positively charged guanidino group of TTX and the negatively charged carboxylate groups
on the side chains at the mouth of the channels.

- Being much larger than the Na+ ions, the bulk of the molecule blocks the entrance to the
Na channel, preventing the flow of Na+ ions until it slowly diffuses off.


"Comparatively smaller hydrated sodium ions versus bulky TTX"

- In addition, TTX has a tenacious hold on the Na channel is further demonstrated by its
occupancy time. Hydrated Na+ ions binds reversibly to the channel on a timescale of
nanoseconds. Comparatively, TTX binds and remains at the Na channel in the order of tens
of seconds.

As a consequence of TTX blockage, sodium ions movement is effectively shut down and the
propagation of action potential ceases. The central and peripheral nervous systems are
impaired, resulting in paralysis and death.

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