A conformational model for the action of general anesthetics at the membrane level. I. Theoretical considerations

Abstract

The first paper of this series describes a working hypothesis for the action of general anesthetics. According to such hypothesis, anesthetics, by inducing a labilisation of lipid-protein interactions in biomembranes, affect the conformation, and hence the activity of membrane-bound catalytic proteins. It is conceivable that such changes in ionic channels in neuronal membranes will abolish the transmission of nervous impulses and give rise to anesthesia. The hypothesis is discussed on the basis of previously known experimental data and of theoretical considerations. Thermodynamic considerations are in favour of the idea that a rupture of lipid-protein interactions will expose protein groups to water destabilising helical structures. A large decrease of alpha-helical content after lipid removal had been previously found. Furthermore lipids affect the kinetics of membrane-bound enzymes, suggesting that conformational changes occur in the catalytic site after lipid removal or perturbation.