Author(s): Colquhoun D, Henderson R, Ritchie JM
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Abstract 1. Tritiated tetrodotoxin has been prepared and purified, and its binding to rabbit, lobster, and garfish non-myelinated nerve fibres examined.2. In each case a component of the binding curve was found that saturated at concentrations of a few nanomolar.3. In addition, non-specific binding, indicated by a linear dependence of the amount bound on concentration, occurred.4. The kinetics of wash-in and wash-out of the radioactive toxin were consistent with a model in which all binding was rapid and reversible and in which diffusion into and out of the nerve bundle was rate-limiting. This was shown by numerical solution of the appropriate non-linear diffusion equation. An extension of the limited biophase model that allows for non-specific binding was shown to give good semiquantitative approximations to the proper diffusion equation; and (unlike the latter) the extension was shown to have a relatively simple solution.5. A number of pharmacological agents were tested for competition with, or perturbation of, tetrodotoxin binding: sodium, calcium and hydrogen ions, lidocaine, batrachotoxin and saxitoxin. Apart from a small calcium effect, only saxitoxin, whose effect on sodium current is similar to that of tetrodotoxin, was found to interfere with binding. Increasing saxitoxin concentrations resulted in reduced amounts of tetrodotoxin binding in a manner consistent with a competition between the two toxins for the same site.
This article was published in J Physiol
and referenced in Journal of Computer Science & Systems Biology