INTERACTION OF INHALED ANESTHETICS WITH MEMBRANE LIPIDS

Binding of Anesthetics to Membrane Lipids

The solubilities of gaseous and volatile agents in membrane lipids tend to correlate with their anesthetic potencies. This correlation is as good^[117] as or better^[90] than that obtained when olive oil is the model solvent. The incorporation of cholesterol into phospholipid model membranes decreases the partitioning of inhaled agents but does not alter the good correlation between anesthetic potency and lipid membrane solubility.^[117] The degree of saturation or length of lipid acyl chains has little effect on the partition coefficient. However, a decrease in temperature increases the partitioning of anesthetics into phospholipid membranes.^[117] At anesthetic concentrations close to 1.0 MAC, lipid membranes contain as many as 80 phospholipid molecules for every anesthetic molecule.^[89]

The interaction of inhaled agents with membrane lipids is a dynamic process, and anesthetic molecules may rapidly exchange between the membrane and aqueous phases. Although anesthetics may penetrate to all depths of the lipid bilayer, there is a preferential anesthetic distribution at the membrane interface^{[118] [119]} where regions of the lipid membrane contact the aqueous environment. In contrast, the nonimmobilizers 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane (see Fig. 4-10 ) exhibit a preferential location in the lipid membrane hydrocarbon core.^{[118] [119] [120]} It has been speculated that the interfacial site may be associated with anesthetic-induced immobility in response to noxious stimuli and that the production of amnesia may be associated with anesthetic penetration into the nonpolar interior of a phospholipid bilayer.^[31]