Effect of Clinical Concentrations of Halothane on Phospholipid-Cholesterol Membrane Fluidity

Wide variation exists among estimates of the concentration of the inhalation anesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in the phospholipid-cholesterol bilayer membrane of a nerve cell exposed to clinical anesthetic concentrations. Attempts to adapt octanol/water partition coefficients to phospholipid-cholesterol bilayer systems, as well as different estimates of the concentration of anesthetic that occur in the lipid region of a nerve cell exposed to a clinical concentration of halothane vapor, have resulted in conflicting conclusions regarding the effects of this anesthetic on nerve membranes. Therefore we have exposed phosphatidylcholine-cholesterol bilayer vesicles to a typical clinical concentration of 1.3% volume of halothane vapor per volume of nitrogen and measured the resultant concentration of halothane in the phospholipid bilayer by gas chromatography. We obtained a value of 30 ± 3 mmoles of halothane per mole of phospholipid-cholesterol for the 1.3% exposure. On the basis of thermodynamic principles of equal chemical potential, we suggest that this concentration obtains in membrane bilayers of the same composition in humans undergoing anesthesia with 1.3% halothane. Electron paramagnetic resonance studies of phospholipid-cholesterol bilayers exposed to concentrations of 1.3% or 3.1% volume of halothane vapor per volume of nitrogen indicate that the internal fluidity of these bilayers is increased following exposure to clinical anesthetic concentrations.