IS THE MECHANISM OF GENERAL-ANESTHESIA RELATED TO LIPID-MEMBRANE SPONTANEOUS CURVATURE

We hypothesize that the mechanism of general anesthesia is via anesthetic-induced alteration of the lipid bilayer lateral tension profile which gives rise to the monolayer spontaneous curvature. The monolayer spontaneous curvature is a compositionally controlled colligative property of lipids which is a measure of the nonlamellar phase tendencies of the system and which characterizes the curvature stress of bilayers. The physical interpretation of this property is discussed. Experiments suggest that the spontaneous curvature of biomembranes is regulated in living cells and that the activities of some integral membrane proteins are sensitive to the magnitude of the property. We explore the possibility that anesthetic action is mediated via anesthetic alteration of the spontaneous curvature of cell membranes and the consequent modulation of membrane protein activity. Although few general anesthetics have thus far been tested for effects on membrane spontaneous curvature, the behavior of n-alkanols appears promising. At physiologically relevant concentrations, n-alkanols significantly alter the spontaneous curvature of model lipid systems. Further, these effects reverse upon application of pressures up to a few hundred atmospheres. Experiments are proposed that would help test the validity of the hypothesis.