The opposing effects of pressure and general anaesthetics on the cation permeability of liposomes of varying lipid composition

Abstract The effect of pressure and general anaesthetics on lipid membranes of different composition was studied by noting the variation in the cation permeability produced in single bilayer liposomes. At concentrations producing a loss of righting reflex in the new Triturus cristatus carnifex the logarithmic of the liposome cation permeability increase was linearly proportional to the concentration of anaesthetic whereas the sugar permeability was generally unaffected. Pressure compensated for the anaesthetic effect by decreasing the membrane cation permeability rather than by removing the anaesthetic from the membrane. The compressibility of the bilayer was estimated as 3·10 −5 atm −1 , similar to but lower than those of non-polar liquids. There was an excellent correlation between the narcotic concentrations required to increase cation permeability through 50% cholesterol liposome membranes and that required to block axonal conduction or protect erythrocytes against hypotonic lysis. The correlation with the isonarcotic concentrations for general anaesthesia was best for the high cholesterol membranes, but in this case the more polar water soluble anaesthetics affected liposome cation permeability too much and non-polar anaesthetics were relatively inactive. This result suggested a site of action for general anaesthesia deeper in the bilayer than the surface region which is known to be rate limiting for liposome cation permeability.