title: Evidence that tetrodotoxin and saxitoxin act at a metal cation binding site in the sodium channels of nerve membrane.
abstract: The effects of monovalent, divalent, and trivalent cations on the binding of tetrodotoxin and saxitoxin to intact nerves and to a preparation of solubilized nerve membranes have been examined. All eight divalent and trivalent cations tested, and the monovalent ions Li(+), Tl(+), and H(+) appear to compete reversibly with the toxins for their binding site. The ability of lithium to reduce toxin binding is paralleled by its ability to reduce tetrodotoxin-sensitive ion fluxes through the nerve membrane. We conclude that the toxins act at a metal cation binding site in the sodium channel and suggest that this site is the principal coordination site for cations (normally Na(+) ions) as they pass through the membrane during an action potential. The dissociation constant for Li(+) is 0.1-0.2 M and for Na(+) > 0.6 M, reflecting the weak binding necessary for rapid passage of sodium ions through the channel.
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D002414:Cations, Monovalent; D005400:Fishes, Poisonous; D066298:In Vitro Techniques; D007700:Kinetics; D008094:Lithium / Q000378:metabolism; D008566:Membranes / Q000378:metabolism; D009832:Olfactory Nerve / Q000378:metabolism*; D011817:Rabbits; D012530:Saxitoxin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D002413:Cations, Divalent; D002414:Cations, Monovalent; D012530:Saxitoxin; D013779:Tetrodotoxin; D008094:Lithium; D012964:Sodium; D002118:Calcium