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

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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.

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