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January 1, 2008Proceedings of the Japan Academy Series B151 citationsOpen Access

Tetrodotoxin -A brief history-

TNToshio Narahashi

Key Points

  • To review the historical discovery of tetrodotoxin (TTX) and describe its specific mechanism of selectively blocking voltage-gated sodium channels.
  • Narrative historical review synthesizing laboratory findings on TTX channel-blocking actions since the early 1960s.
  • Analysis of physiological mechanisms concerning TTX binding to the outer nerve membrane and its ecological food chain origin.
  • TTX acts exclusively from the extracellular surface to bind the selectivity filter of voltage-gated sodium channels, preventing sodium ion flow without altering the gating mechanism.
  • The compound exhibits strict selectivity for voltage-gated sodium channels without affecting other ion channels or receptor systems, facilitating the identification of TTX-resistant channels involved in pain pathways.

Abstract

Tetrodotoxin (TTX), contained in puffer, has become an extremely popular chemical tool in the physiological and pharmacological laboratories since our discovery of its channel blocking action in the early 1960s. This brief review describes the history of discovery of TTX action on sodium channels, and represents a story primarily of my own work. TTX inhibits voltage-gated sodium channels in a highly potent and selective manner without effects on any other receptor and ion channel systems. TTX blocks the sodium channel only from outside of the nerve membrane, and is due to binding to the selectivity filter resulting in prevention of sodium ion flow. It does not impairs the channel gating mechanism. More recently, the TTX-resistant sodium channels have been discovered in the nervous system and received much attention because of their role in pain sensation. TTX is now known to be produced not by puffer but by bacteria, and reaches various species of animals via food chain.(Communicated by Masanori OTSUKA, M.J.A.).

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Cite This Study

Toshio Narahashi (2008) studied this question.

synapsesocial.com/papers/6a0f0847b7cc3b883f22fefdhttps://doi.org/10.2183/pjab.84.147
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