Physical parameters of the anesthetic site

Abstract

Theoretical consideration of the interaction between induced dipoles and a field of force composed of ionic, dipole and London forces are presented. The analysis as applied to the phenomena of general anesthesia allows characterization of the anesthetic site with three physical parameters: (1) the cohesive energy of the site, E c, (2) the adhesive contribution to the enthalpy of solution, A, and (3) the Barclay-Butler B coefficient. Their values are 13694 cal/mol, 299 ( cal/mol) 1 2 and 0.00237 K −1, respectively. All these values are much higher than the measured values of these same parameters, using noble gases, in dimyristoyl phosphatidylcholine bilayers above their phase transition temperature and the bulk organic liquid, benzene. The relatively large values of the adhesive term and Barcley-Butler B coefficient imply that the anesthetic site is quite hydrophilic in nature in the sense that it likely possesses a formal charge. The large value of the cohesive energy of the site suggests that the site may either be a boundary lipid or a protein (which we cannot distinguish between) but it is definitely not, for these gases, like a simple lipid bilayer above its transition temperature or like benzene. An extension of the molecular interpretation of selectivity, that includes other interactions besides the London-Van der Waals type is presented. The selectivity (at constant temperature) is determined by the adhesive term and the Barclay-Butler B coefficient. Using this analysis we found that synapses but not axons exhibit the same selectivity as the anesthetic site. This implies that the synapse is clearly the model to study in attempting to elucidate molecular mechanisms of anesthesia.