The Nature of The Site of General Anesthesia

Abstract

Publisher Summary This chapter chapter discusses that both lipids and proteins, and their complexes, interact with general anesthetics. In both the cases, there are model systems where interactions correlate with anesthetic potency as well as other model systems where they do not. Of the lipid bilayers, those with a high ratio of cholesterol to phospholipid appear to fare best, while of the proteins, the luciferases offer the most tested and successful model. The functional changes resulting from anesthetic-lipid or anesthetic- protein interactions provides another clue to the importance of each in producing general anesthesia. The changes induced in lipid bilayers at clinical doses are small and seem unlikely per se to result in physiological effects. Most lipid theories of anesthesia have assumed that perturbation of lipid-protein interactions underlies anesthetic action. The systematic studies of average bilayer properties such as volume, order or fluidity support the lipid hypothesis in a general way, but which fail to directly address the mechanistic link with protein function. As the knowledge of membranes has increased, it has become more clear that average lipid parameters of this sort are less likely to be related to membrane protein function than are the detailed heterogeneous arrangement of lipids and proteins. In this sense, the study of these anesthetic mechanisms is in a transition between thermodynamic and molecular explanations.