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.
