R Bains1, M C Moe, M L Vinje, J Berg-Johnsen. 1. Department of Neurosurgery, Institute for Surgical Research, Rikshospitalet HF, Oslo, Norway. r.s.bains@klinmed.uio.no
Abstract
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 Ca(2+) concentration [Ca(2+)](i) and the mitochondrial membrane potential (DeltaPsi(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 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 microM. The effect on the electron transport chain was investigated by blocking complex V. RESULTS: Sevoflurane and propofol decreased DeltaPsi(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 microM. Neither sevoflurane nor propofol affected [Ca(2+)](i) significantly. Sevoflurane and propofol decreased DeltaPsi(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.
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 Ca(2+) concentration [Ca(2+)](i) and the mitochondrial membrane potential (DeltaPsi(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 ([Ca(2+)](i)) and JC-1 (DeltaPsi(m)) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 microM. The effect on the electron transport chain was investigated by blocking complex V. RESULTS:Sevoflurane and propofol decreased DeltaPsi(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 microM. Neither sevoflurane nor propofol affected [Ca(2+)](i) significantly. Sevoflurane and propofol decreased DeltaPsi(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.