Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms

Background and objectives The mitochondrial membrane potential drives the main functions of the mitochondria. Sevoflurane depolarizes neural mitochondria. There is still, however, limited information concerning the effect of anaesthetics on neural mitochondria in humans. The effect of sevoflurane and propofol on the intracellular Ca2+ concentration [Ca2+](i) and the mitochondrial membrane potential (delta Psi(m)) was therefore compared in rat and human synaptosomes, and the changes were related to interventions in the electron transport chain. Methods Synaptosomes from rat and human cerebral cortex were loaded with the fluorescent probes fura-2 ([Ca2+](i)) and JC-1 (delta Psi(m)) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 mu M. The effect on the electron transport chain was investigated by blocking complex V. Results Sevoflurane and propofol decreased delta Psi(m) in rat synaptosomes in a dose-dependent manner, and to the same extent by equipotent doses. Inhibition of complex V enhanced the depolarizing effect of sevoflurane 2 MAC, but not of propofol 100 mu M. Neither sevoflurane nor propofol affected [Ca2+](i) significantly. Sevoflurane and propofol decreased delta Psi(m) in human synaptosomes to the same extent as in the rat experiments. Conclusions Sevoflurane and propofol at equipotent doses depolarize the mitochondria in rat and human nerve terminals to the same extent. The depolarizing effect of propofol on Psi(m) was more rapid in onset than that of sevoflurane. Whereas sevoflurane inhibits the respiratory chain sufficiently to cause ATP synthase reversal, the depolarizing effect of propofol seems to be related to inhibition of the respiratory chain from complex I to V.