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Sevoflurane depolarizes pre‐synaptic mitochondria in the central nervous system
Author(s) -
Moe M. C.,
Bains R.,
Vinje M. L.,
Larsen G. A.,
Kampenhaug E. B.,
BergJohnsen J.
Publication year - 2004
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.1399-6576.2004.00382.x
Subject(s) - medicine , sevoflurane , central nervous system , mitochondrion , neuroscience , nervous system , anesthesia , biochemistry , psychiatry , chemistry , biology
Background: Volatile anaesthetics protect the heart from ischaemic injury by activating mitochondrial signalling pathways. The aim of this study was to test whether sevoflurane, which is increasingly used in neuroanaesthesia, affects mitochondrial function in the central nervous system by altering the mitochondrial membrane potential (ΔΨ m ). Methods: In order to correlate free cytosolic Ca 2+ ([Ca 2+ ] i ) and ΔΨ m , rat neural presynaptic terminals (synaptosomes) were loaded with the fluorescent probes fura‐2 and JC‐1. During sevoflurane exposure, 4‐aminopyridine (4‐AP) 500 µM to induce pre‐synaptic membrane depolarization or carbonylcyanide‐p‐(trifluoromethoxy)‐phenylhydrazone (FCCP) 1 µM to induce maximum mitochondrial depolarization was added. In order to block mitochondrial ATP‐regulated K + ‐channels (mitoK ATP ), the antagonist 5‐hydroxydecanoate (5‐HD) 500 µM was added. Results: In Ca 2+ ‐containing medium, both sevoflurane 1 and 2 MAC gradually decreased the normalized JC‐1 ratio from 0.96 ± 0.01 in control to 0.92 ± 0.01 and 0.89 ± 0.01, representing a depolarization of ΔΨ m ( n = 9, P < 0.05). Sevoflurane 2 MAC increased [Ca 2+ ] i . In Ca 2+ ‐depleted medium, sevoflurane 1 and 2 MAC depolarized ΔΨ m , while [Ca 2+ ] i remained unaltered. Sevoflurane 2 MAC attenuated the 4‐AP‐induced depolarization of ΔΨ m . When mitoK ATP was blocked, the sevoflurane‐induced depolarization of ΔΨ m was attenuated, but not blocked. The depolarizing effect of sevoflurane on ΔΨ m compared with FCCP was calculated to 13.2 ± 1.3% in Ca 2+ ‐containing and 15.1 ± 1.2% in Ca 2+ ‐depleted medium ( n = 7). Conclusions: Sevoflurane depolarizes ΔΨ m in rat synaptosomes, and the effect is not dependent on Ca 2+ ‐influx to the cytosol. Opening of mitoK ATP is partly responsible for the depolarizing effect of sevoflurane.