Interactions between anaesthetics and lipid mixtures. Amines.

The effect of a number of amine anaesthetics related to procaine on the temperature of lipid phase transitions has been studied using chlorophyll a as a fluorescence probe. The amines cause a reduction in the temperature of the phase transition of dipalmitoyl phosphatidylcholine and dipalmitoyl phosphatidylethanolamine and of mixtures of these lipids. The binding of charged amines causes a build up of positive charge on the membranes, limiting the binding. Incorporation of negative charge into the lipid bilayers causes a considerable increase in the binding of the charged amines, and the effect is reversed by addition of Ca2+. Anaesthesia is suggested to arise from an increase in the proportion of lipid in the liquid crystalline phase, resulting in a conformational change in the sodium channel. Effects of the tertiary amines on nerve conduction can be understood if the negatively charged lipid in the membrane is concentrated around the sodium channel: positively charged anaesthetics will have a greater effect when applied to the inside of a nerve because of the low Ca2+ concentration inside the nerve.