Effects of the general anaesthetic Propofol on the Ca2+‐induced permeabilization of rat liver mitochondria

Abstract

The molecular mechanisms of the Ca²⁺-induced permeabilization of rat liver mitochondria was evaluated by studying a new effect of the commonly used general anaesthetic Profol(2,6-diisopropylphenol). The compound was found to induce an apparent uptake of Ca²⁺ at steady-state in the Ca²⁺-distributed between the medium and the mitochondria, and to inhibit swelling and release of accumulated Ca²⁺ induced by inorganic phosphate, t-butyl hydroperoxide, diamide or FCCP plus Ruthenium red. The compound did not stimulate the activity of the Ca²⁺-uniporter and it is concluded that the effects seen are due to the inhibition of the Ca²⁺-dependent, unspecific permeability increase. The results suggest two mechanisms whereby Propofol stabilizes the mitochondrial membrane in the presence of Ca²⁺: (i) by interaction with the putative pore, thus causing its closure; and (ii) by scavenging of free radicals thus inhibiting its opening during oxidative stress.