Alcohol effects on lipid bilayer permeability to protons and potassium: relation to the action of general anesthetics.

Past work has shown that general anesthetics perturb the membranes of isolated synaptic vesicles, thereby increasing permeability to protons and inhibiting the ability of the vesicles to take up catecholamines. It has been proposed that such effects may produce anesthesia through inhibition of synaptic transmission. The mechanisms of perturbation is unknown. Two possible explanations include alterations of dielectric constant or production of defects as anesthetics partition into the bilayer phase. In order to choose between these alternatives, we measured the effect of nine alcohols and two alkanes on liposome permeability to protons and potassium. Ionic permeability was increased by alcohols and alkanes to similar degrees, thereby ruling out direct effects on the membrane dielectric constant caused by partitioning of anesthetics into the bilayer. Other experiments confirmed earlier reports that the enhanced permeability caused by anesthetics is not specific for protons. We conclude that these membrane perturbants act by increasing the number of transient, ion-conducting defects normally present in the bilayer structure.