Temperature-dependence of the action of nerve blocking agents and its relationship to membrane-buffer partition coefficients: thermodynamic implications for the site of action of local anaesthetics.

The local anaesthetic action of a series of nerve blocking agents was examined at temperatures between 4 degrees C and 20 degrees C in isolated sciatic nerves from cold-adapted frogs. Cooling alone had little effect on the amplitude of the action potential but the conduction velocity was decreased and the duration increased. Cooling had little effect on the local anaesthetic action of the short chain alkanols but that of the long chain alkanols, benzyl alcohol, benzocaine and pentobarbitone was markedly enhanced. The partition of both short and long chain alkanols and of pentobarbitone into a liposome suspension of similar composition to axonal membrane lipids was reduced by cooling from 40 degrees C to 4 degrees C. The results are not compatible with the lipid hypotheses of anaesthetic action. The implications for the nature of the site of action are discussed.