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

There appear to be four distinct comicentration-dependent effects of halothane (2-bronmo-2-chloro-1, 1, 1-trifluoroethane) upon mitochondria. First, at low conceimtration (0.5-2.0 in the gas phase) there is a rapidly appearing, rapidly reversible effect on electroim transport in the region of NADH dehydrogenase. Oxidation with succilmate does not appear to be altered in this concentration range. Second, a small but distinct immcrease in respiration and a significant inhibition of the rate of phosphate-induced swelliimg with succinate as substrate suggest a limited uncoupling by 0.5-2.0 % levels of haiothane. The degree of ummcoupling appears to be greater at 3-4 % haiothaime. Third, at higher thaim clinical anesthetic concen-trations (3-4%) there is partial inhibition of succinate oxidation. Most of this effect is prob-ably direct, since oxidation is not restored to normal by the addition of 2, 4-dimmitropimenol and other uncoupling agents. Fourth, halothane in coimcentrations between 3 aimd 10 % alters the membrane permeability and causes energy-independent swelling of mitochommdria, but does not appear to cause complete disintegration of the membrane