Produced by symbiotic bacteria (such as Pseudoalteromonas, Pseudomonas, and Vibrio) and accumulated in pufferfish (Tetraodontiformes), blue-ringed octopuses, and rough-skinned newts, tetrodotoxin had its selective sodium-channel block demonstrated in 1964 by Toshio Narahashi and John W. Moore using voltage clamp.
Its positively charged guanidinium group plugs the outer vestibule of the sodium channel selectivity filter at single-digit nanomolar concentrations, completely abolishing action potential firing in nerves and skeletal muscle without affecting potassium channels.
In electrophysiology, TTX pharmacologically separates TTX-sensitive sodium channels (such as Nav1.7 / SCN9A) from TTX-resistant nociceptive and cardiac isoforms (Nav1.8 / SCN10A, Nav1.9 / SCN11A, and Nav1.5 / SCN5A).