Molecular Pharmacology, Vol 8, 285-292, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

The Kinetics of the Interaction between Tetrodotoxin and Mammalian Nonmyelinated Nerve Fibers

¹ Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

Kinetic measurements were made of the blockade by tetrodotoxin (TTX) of sodium channels in the nonmyelinated fibers of the desheathed rabbit vagus nerve. The onset rate was found to increase with TTX concentration, whereas the offset rate after removal of TTX was found to be relatively independent of the TTX concentration to which the preparation had been exposed. It has been shown that the rate of action of tetrodotoxin may well be controlled by diffusion (slowed by simultaneous adsorption) rather than by the rate of the drug-receptor interaction. Nevertheless, the equilibrium constant calculated independently from kinetic measurements, on the wrong assumption that the rates are controlled by the drug-receptor interaction, should be roughly correct. The equilibrium constant so calculated was 3.18 nM, confirming the previous independent estimate made from equilibrium measurements of TTX blockade.