Effect of clinical concentrations of halothane on phospholipid-cholesterol membrane fluidity
Mastrangelo, C.J.; Trudell, J.R.; Edmunds, H.N.; Cohen, E.N.
Molecular Pharmacology 14(3): 463-467
1978
ISSN/ISBN: 0026-895X PMID: 661814 Document Number: 126476
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/H2O 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. Phosphatidylcholine-cholesterol bilayer vesicles were exposed to a typical clinical concentration of 1.3% volume of halothane vapor/volume of N and measured the resultant concentration of halothane in the phospholipid bilayer by gas chromatography. A value of 30 .+-. 3 mmoles of halothane/mol of phospholipid-cholesterol was obtained for the 1.3% exposure. On the basis of thermodynamic principles of equal chemical potential, this concentration may be obtained in membrane bilayers of the same composition in humans undergoing anesthesia with 1.3% halothane. EPR studies of phospholipid-cholesterol bilayers exposed to concentrations of 1.3% or 3.1% volume of halothane vapor/volume of N indicate that the internal fluidity of these bilayers is increased following exposure to clinical anesthetic concentrations.