Is the mechanism of general anesthesia related to lipid membrane spontaneous curvature?

Abstract

Lipid bilayers in biomembranes may exist in a state of elastic curvature stress which may couple to the conformation of integral membrane proteins in a logical, and energetically significant, fashion. Many biomembranes contain sufficiently large fractions of nonlamellar-prone lipids to have monolayers under substantial curvature stress. Although very few experiments have been performed that can be used to correlate protein activity with curvature stress, the literature does contain a small number of studies that indicate that some protein function is nonspecifically modulated by the amounts of nonlamellar-prone lipid in the imbedding bilayers. The spontaneous curvature, is altered by the presence of anesthetics in physiologically relevant concentrations. This leads us to suggest that anesthetic action may be coupled to protein function via alteration of the tensions leading to the spontaneous curvature of biomembrane layers. The spontaneous curvature is also sufficiently sensitive to pressure that a mechanism for the pressure reversal of anesthesia follows if the effects of pressure are to counter changes in membrane lateral tension induced by anesthetics. It is emphasized that many more experimental data must be acquired to determine whether the ideas presented in this paper have validity. In particular, there is a need for data on the effects of different anesthetics and pressure on the spontaneous curvature and, more generally, lipid monolayer lateral tensions. Most importantly, experiments must be performed to investigate whether protein function correlates with these quantities.