Molecular Basis for Unitary Theories of Inhalation Anaesthesia

Abstract

Recent knowledge of the molecular structure of nerve cell membranes provides a basis for understanding and discussing unitary mechanisms of anaesthesia. A unitary mechanism is a general mechanism by which any of the many forms of inhalation anaesthetic may alter many of the functions of the nervous system. The wide variety of molecular shapes and sizes of anaesthetics that produce general anaesthesia at equimolar membrane concentrations, and the diversity of nervous, muscular, respiratory, and cardiovascular effects, argue for a unitary mechanism of anaesthesia. My discussion of theories of anaesthesia will be in three parts. First, I will review the current knowledge of the molecular structure of the phospholipid bilayer membranes that surround the function-controlling proteins of the nerve cell. Secondly, I will describe research on molecular mechanisms of anaesthesia performed during the last 10 years. I will concentrate my discussion on theories that involve perturbations of phospholipid-protein interactions by inhalation anaesthetics. Finally, I will present a new model system developed by Galla and myself for studying the effect of inhalation anaesthetics on a protein-induced lateral phase separation.