title: Sevoflurane reduces synaptic glutamate release in human synaptosomes.
abstract: Volatile anesthetics reduce excitatory synaptic transmission in the mammalian brain. In the present study, the effect of sevoflurane on synaptic glutamate release, free cytosolic Ca2+ ([Ca2+]i), and glutamate uptake was investigated using isolated presynaptic terminals prepared from human cerebral cortex. The tissue was obtained from standard temporal lobe specimens removed because of epilepsy. The glutamate release and [Ca2+]i was measured as the fluorescence of nicotinamide adenine dinucleotide phosphate (NADPH) and fura-2, respectively. The uptake of radiolabeled glutamate was measured in a beta-scintillation counter. Membrane depolarization with 4-aminopyridine for three minutes evoked a Ca2+-dependent glutamate release of 3.4 +/- 0.5 nmol/mg. Sevoflurane 2.5 and 4.0% attenuated the evoked release by 45 and 55%, respectively. The evoked increase in [Ca2+]i was not significantly altered by the anesthetic agent. The uptake studies were performed in the high-affinity area, and Km was calculated to 19.3 +/- 5.7 x 10(-6) M and Vmax to 5.7 +/- 1.0 micromol g(-1) min(-1). The Km and Vmax values were not significantly altered by sevoflurane 2.5%. These results demonstrate that sevoflurane in the human brain reduces Ca2+-dependent glutamate release. The exact mode of action is still to be resolved.
authors.affiliation: Institute for Surgical Research and Department of Neurosurgery, Rikshospitalet University Hospital, Oslo, Norway.
authors.forename: Morten C
authors.initials: MC
authors.lastname: Moe
authors.forename: Jon
authors.initials: J
authors.lastname: Berg-Johnsen
authors.forename: Geir A
authors.initials: GA
authors.lastname: Larsen
authors.forename: Geir K
authors.initials: GK
authors.lastname: Røste
authors.forename: Morten L
authors.initials: ML
authors.lastname: Vinje
mesh_terms: D015761:4-Aminopyridine / Q000378:metabolism; D000328:Adult; D018685:Anesthetics, Inhalation; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000601:surgery; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008738:Methyl Ethers; D000077149:Sevoflurane; D013569:Synapses / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D013702:Temporal Lobe / Q000601:surgery
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D018698:Glutamic Acid; D015761:4-Aminopyridine; D002118:Calcium