title: Volatile anesthetics depress Ca2+ transients and glutamate release in isolated cerebral synaptosomes.
abstract: BACKGROUND
  The current study was performed to determine whether volatile anesthetics may include as part of their action in the central nervous system the depression of presynaptic transmitter release by alteration in intrasynaptic [Ca2+] ([Ca2+]i).
  
  
  METHODS
  Guinea pig cerebrocortical synaptosomes were studied at 37 degrees C suspended in control buffer solution containing 1.3 mM external [Ca2+] ([Ca2+]e). Spectrofluorometric assays were used to monitor [Ca2+]i with the Ca(2+)-sensitive fluorophore Fura-2 and to monitor glutamate release with an enzyme-coupled assay that produced the fluorescent product nicotinamide adenine dinucleotide phosphate. To activate the increase in [Ca2+]i and glutamate release, synaptosomes were depolarized by abruptly increasing external [K+] from 5 to 35 mM. Responses were determined in solutions equilibrated with approximately 1 or 2 minimum alveolar concentration (MAC) isoflurane, enflurane, or halothane and also in solutions with decreased [Ca2+]e (0.025, 0.05, 0.1, 0.2, 0.4, and 0.6 mM).
  
  
  RESULTS
  Although they had no action on basal behavior, the anesthetics depressed the K(+)-depolarization-induced increase in both [Ca2+]i and glutamate release in a dose-dependent fashion. The [Ca2+]i transient was inhibited by 13-21% per MAC, and glutamate release was depressed 14-28% per MAC. The depression of both [Ca2+]i and glutamate release caused by 2.5% isoflurane, 3.4% enflurane, and 1.5% halothane could be reproduced by a reduction in [Ca2+]e to 0.2-0.4 mM.
  
  
  CONCLUSIONS
  In this setting, isoflurane, enflurane, and halothane decrease [Ca2+]i in a manner consistent with inhibition of Ca2+ entry, possibly by specific voltage-gated neuronal Ca2+ channels. This decrease in [Ca2+]i is sufficient to account for all or most of the associated decrease in glutamate release.
authors.affiliation: Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: N
authors.initials: N
authors.lastname: Miao
authors.forename: M J
authors.initials: MJ
authors.lastname: Frazer
authors.forename: C
authors.initials: C
authors.lastname: Lynch
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects; D002352:Carrier Proteins / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D011189:Potassium Chloride / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013574:Synaptosomes / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D018698:Glutamic Acid; D011189:Potassium Chloride; D002118:Calcium