Anesthesia: An interfacial phenomenon

Abstract

The research on the anesthesia mechanism is unique in that a concerted consensus has never been reached. Nonspecific interaction with hydrophobic parts of cell membranes is favored by many, but specific binding to receptor proteins is also proposed. This article limits its discussion on the nonspecific aspect of volatile anesthetic actions. There are two features in anesthesia that involve colloid and surface chemistry. (1) Anesthesia can be induced by any small lipid-soluble molecules that perturb macromolecular structure. (2) A pressure of about 100 atm completely antagonizes anesthetic actions. According to the Le Chatelier principle, the system volume of anesthetized state is larger than the awake state. The volume increase is not caused by the space occupied by the bound anesthetic molecules, but is created in excess of the membrane volume plus the bound anesthetic molecules. The origin of this excess volume is the key to understand anesthesia mechanisms. Among the multiple factors that contribute to creation of the excess volume, the interfacial properties of membranes and proteins are considered to contribute most. This is because the interfacial water molecules are almost maximally compressed by the surface charges and are denser than the bulk water. When these close-packed water molecules are released into the bulk, the system volume expands with creation of an extra volume. The relative increase in the hydrophobicity of the water-macromolecule interface may be the cause of anesthesia.