Effects of small nonpolar molecules on membrane compressibility and permeability. A theoretical study of the effects of anesthetic gases.

We explore from a theoretical perspective the effects of small nonpolar molecules, such as anesthetic gases, on membrane compressibility and permeability. As a model system we expand a previously proposed generalization of Nagle's model for biomembrane phase transitions. In this model anesthetic gases alter membrane compressibility, causing profound changes in membrane permeability. Anesthetics either increase or decrease membrane permeability, depending on whether the membrane lipid is originally in the solid or melted state, or in a two-phase region. These changes are reversed by high pressure, in agreement with experimental results. Anesthetic-induced changes in compressibility are predicted to inhibit fusion of phospholipid vesicles to each other and to planar bilayers, and thus might be expected to inhibit the fusion of presynaptic vesicles with the presynaptic nerve membrane. This work provides a detailed molecular theory for many of the effects of anesthetic gases on both synapse and axon, and provides a coherent framework for understanding diverse experimental results.