Abstract
Tetrodotoxin and saxitoxin are small, compact asymmetrical marine toxins that block voltage-gated Na channels with high affinity and specificity. They enter the channel pore’s outer vestibule and bind to multiple residues that control permeation. Radiolabeled toxins were key contributors to channel protein purification and subsequent cloning. They also helped identify critical structural elements called P loops. Spacial organization of their mutation-identified interaction sites in molecular models has generated a molecular image of the TTX binding site in the outer vestibule and the critical permeation and selectivity features of this region. One site in the channel’s domain I P loop determines affinity differences in mammalian isoforms.
Highlights
Tetrodotoxin (TTX) and saxitoxin (STX)—guanidinium toxins—are potent and potentially lethal marine toxins with features that have been of great value to ion channel research
The guanidinium toxins bind with high affinity deeply within the voltage-gated Na channel’s outer vestibule through multiple interactions to carboxylates and other residues
The binding is selective for voltage-gated Na channels, and this property has made radio labeled toxin crucial in the channel’s cloning
Summary
Tetrodotoxin (TTX) and saxitoxin (STX)—guanidinium toxins—are potent and potentially lethal marine toxins with features that have been of great value to ion channel research. The two toxins are small molecules with similar structural properties and they block voltage-gated Na channels competitively Because of their specificity for Na channels they allow separation of Na currents from other ionic currents in native cells. After Narahashi and colleagues [3,4] had shown that TTX blocked voltage-dependent Na currents, Hille [5] determined a number of important pharmacological characteristics He confirmed that TTX and STX appeared to be completely specific for Na channels and bound with 1:1 stoichiometry. Ca2+ competes with TTX/STX and it blocks within the membrane electric field at the same apparent depth as TTX/STX These arguments are all inferential, but they have been valuable guides to experimental study of the toxin binding site. In addition there is an unconfirmed report that one isoform group of the T type Ca channel (Cav3) binds TTX and STX and is blocked with low toxin affinity [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
