The Mechanism of the Halothane-Dependent Efflux of Calcium from Rat-Liver Mitochondria.

The halothane-dependent, calcium-induced loss of respiratory control in rat liver mitochondria [1,2] is Mg²⁺-dependent and is accompanied by an enhanced mitochondrial swelling. It is suggested that this swelling reflects an increase in calcium activity in the matrix space, due to a decrease in binding of the accumulated cation. This change in the partition of intramitochondrial calcium is correlated with an inhibition by halothane of energy-independent, calcium-induced swelling. The enhanced swelling associated with the active accumulation of calcium in the presence of halothane does not lead to a marked increase in permeability to other ions. Nevertheless, under conditions of energised calcium uptake, and in the presence of Mg²⁺, a halothane-dependent, ruthenium red-insensitive efflux of calcium is observed. This is consistent with the proposed halothane- dependent increase in the matrix activity of accumulated Ca²⁺. It is suggested that this mechanism accounts for the previously postulated [2] futile cycle of calcium uptake and release induced by halothane in rat liver mitochondria. [ABSTRACT FROM AUTHOR]