Molecular Pharmacology, Vol 6, 67-77, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Halothane on Electron Transport, Oxidative Phosphorylation, and Swelling in Rat Liver Mitochondria

¹ Edward Mallinckrodt Department of Pharmacology and Division of Anesthesiology, Department of Surgery Washington University School of Medicine, St. Louis, Missouri 63110

There appear to be four distinct concentration-dependent effects of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) upon mitochondria. First, at low concentration (0.5-2.0% in the gas phase) there is a rapidly appearing, rapidly reversible effect on electron transport in the region of NADH dehydrogenase. Oxidation with succinate does not appear to be altered in this concentration range. Second, a small but distinct increase in respiration and a significant inhibition of the rate of phosphate-induced swelling with succinate as substrate suggest a limited uncoupling by 0.5-2.0% levels of halothane. The degree of uncoupling appears to be greater at 3-4% halothane. Third, at higher than clinical anesthetic concentrations (3-4%) there is partial inhibition of succinate oxidation. Most of this effect is probably direct, since oxidation is not restored to normal by the addition of 2,4-dinitrophenol and other uncoupling agents. Fourth, halothane in concentrations between 5 and 10% alters the membrane permeability and causes energy-independent swelling of mitochondria, but does not appear to cause complete disintegration of the membrane.