The interaction at equilibrium between tetrodotoxin and mammalian non-myelinated nerve fibres

Abstract

1. As a preliminary to chemical studies an estimate has been made of the equilibrium dissociation constant (K) for the interaction of tetrodotoxin (TTX) with the non-myelinated fibres of the rabbit desheathed vagus nerve.2. TTX causes a parallel shift to the right of the curves obtained when either the height or the conduction velocity of the compound action potential are plotted against the logarithm of the external sodium concentration.3. A model has been formulated based on the independence principle and the Hodgkin-Huxley theory, and the experimental results shown to be consistent with it. On this basis, and on the assumptions that one TTX molecule blocks one sodium channel, and that binding is Langmuir, K was estimated to be about 3-5 nM at about 20 degrees C. Other simple non-Langmuir models gave essentially similar low values for K.4. An alternative method of computing K that makes rather different assumptions gives a similar low value.5. Despite the low value for K, a TTX concentration of at least 100 nM is needed to block conduction completely and this seems to be related to the fact that conduction is not completely blocked until the external sodium concentration falls below 7% of its value in normal Locke.6. The minimum sodium concentration needed to support conduction increased with temperature.