Do anesthetics fluidize membranes?

Abstract

The so-called membrane fluidizing effect of anesthetics as a cause of anesthesia has been questioned, mainly because the magnitude of the increase in "fluidity" is insignificant at clinically relevant anesthetic pressures. However, the term "fluidity" has an unfortunate history of being misrepresented in membrane biology. It is often expressed as the ease of movement of probe molecules incorporated into the hydrophobic region of the membrane, thereby representing the property of the microenvironment where the probe molecules reside. In surface chemistry, "membrane fluidity" means inverse viscosity. Membrane viscosity is an integral property of a total membrane (not a part of membrane), and membrane molecules must dislocate and flow against resistance. The ease of motion of probe molecules, therefore, is not fluidity, and is now expressed by the order parameter. The present study measured the effect of halothane on surface viscosity of a phospholipid monolayer spread on a water surface by an oscillating pendulum surface viscometer. The results indicate a significant decrease of about 31% in the surface viscosity by the clinical pressure of halothane; anesthetics do fluidize membranes. Two factors contribute to the surface viscosity of the lipid monolayer; the property of the membrane proper (association between phospholipid molecules) and dragging of water (association between phospholipid and water molecules). The association between phospholipid molecules is in large part related to the order parameter. The fact that anesthetics show little effect on the order parameter, whereas halothane shows a significant effect on the membrane viscosity, indicates that halothane releases surface-bound water. It is postulated that the primary effect of anesthetics on membranes is to weaken the lipid-water interaction forces.