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Sevoflurane and propofol depolarize mitochondria in rat and human cerebrocortical synaptosomes by different mechanisms
Author(s) -
BAINS R.,
MOE M. C.,
VINJE M. L.,
BERGJOHNSEN J.
Publication year - 2009
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2009.02047.x
Subject(s) - sevoflurane , propofol , depolarization , mitochondrion , membrane potential , biophysics , mitochondrial respiratory chain , synaptosome , pharmacology , medicine , anesthesia , biochemistry , chemistry , biology , central nervous system , endocrinology
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 (ΔΨ 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 (ΔΨ m ) before exposure to sevoflurane 1 and 2 minimum alveolar concentration (MAC), and propofol 30 and 100 μM. The effect on the electron transport chain was investigated by blocking complex V. Results: Sevoflurane and propofol decreased ΔΨ 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 μM. Neither sevoflurane nor propofol affected [Ca 2+ ] i significantly. Sevoflurane and propofol decreased ΔΨ 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 Ψ 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.