Sevoflurane depolarizes pre-synaptic mitochondria in the central nervous system

• Published in: Acta anaesthesiologica Scandinavica 2004-05, Vol.48 (5), p.562-568
• Main Authors: Moe, M. C., Bains, R., Vinje, M. L., Larsen, G. A., Kampenhaug, E. B., Berg-Johnsen, J.
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - administration & dosage; Adenosine Triphosphate; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Inhalation - pharmacology; Animals; Anti-Arrhythmia Agents - administration & dosage; Biological and medical sciences; Carbonyl Cyanide m-Chlorophenyl Hydrazone - administration & dosage; Carbonyl Cyanide m-Chlorophenyl Hydrazone - analogs & derivatives; Cells, Cultured; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; CNS; Decanoic Acids - administration & dosage; Female; Fluorescence Polarization; Hydroxy Acids - administration & dosage; Medical sciences; Membrane Potentials - drug effects; Membrane Proteins - drug effects; Methyl Ethers - pharmacology; Mitochondria - drug effects; Mitochondria - physiology; mitochondrial membrane potential; mitoKATP; Potassium Channel Blockers - administration & dosage; Potassium Channels; Presynaptic Terminals - drug effects; Rats; Rats, Wistar; sevoflurane; synaptosomes; Synaptosomes - drug effects; Time Factors; volatile anesthetics
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/j.1399-6576.2004.00382.x

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 (ΔΨm). Methods:  In order to correlate free cytosolic Ca2+ ([Ca2+]i) and ΔΨm, 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 (mitoKATP), the antagonist 5‐hydroxydecanoate (5‐HD) 500 µM was added. Results:  In Ca2+‐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 ΔΨm (n = 9, P