Effect of a local anaesthetic on hydrocarbon chain order in membranes [21]

THE mode of action of anaesthetics has provoked considerable interest and speculation^1,2. For tetrodotoxin³, it is clear that direct interaction of the anaesthetic with the sodium channel blocks nerve conduction; in other cases changes in lipid bilayer structure, such as membrane expansion², fluidus expansion¹ or surface-charge modulation⁴, have been invoked. Recently, a mechanism involving an increase in lipid bilayer thickness has been suggested from results obtained using black film techniques^5-7. We have investigated the hydrocarbon chain length of a lecithin bilayer in the presence and absence of the anaesthetic benzyl alcohol^8,9 using high-field deuterium nuclear magnetic resonance (NMR) spectroscopy of specifically deuterated lipids ^10-16, to determine the changes in bilayer structure that occur on addition of the anaesthetic alcohol. We report here that at concentrations used for local anaesthesia there is no change in membrane thickness. By comparison, cholesterol (at 0.3 mol fraction) causes an ∼0.46 nm increase in membrane thickness. We therefore suggest that the amount of solvent (tetradecane) in black lipid membranes, and hence their thickness, may be influenced by the presence of benzyl alcohol and cholesterol⁵.