A unitary theory of anesthesia based on lateral phase separations in nerve membranes

This paper relates research on anesthetic effects on lipid membrane systems to mechanisms of neural function. A unitary theory of anesthesia based on anesthetic-induced changes in fluid-solid-phase separations in the lipid region of nerve membranes is presented. It is suggested that anesthetics act by fluidizing nerve membranes to a point where critical lipid regions no longer contain phase separations. As a consequence, the membranes are less able to facilitate the conformational changes in proteins that may be the basis for such membrane events as ion gating, synaptic transmitter release, and transmitter binding to receptors. It is proposed that the anesthetic-modified phase separation behavior of the membrane may alter neural function by a combination of the following effects: inhibition of conformational changes of intrinsic membrane proteins; prevention of the association of protein subunits to form polymeric ion channels; depression of transmitter release by preventing fusion of vesicles containing synaptic transmitter with the membrane of the presynaptic terminal.