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Molecular Pharmacology, Vol 14, 463-467, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

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

C. J. MASTRANGELO 1, J. R. TRUDELL 1, H. N. EDMUNDS 1, and E. N. COHEN 1

1 Department of Anesthesia, Stanford University School of Medicine, Stanford, California 94305

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.

Submitted on September 6, 1977
Accepted on December 21, 1977




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