Volatile anesthetic effects on glutamate versus GABA release from isolated rat cortical nerve terminals: basal release

J Pharmacol Exp Ther. 2006 Jan;316(1):208-15. doi: 10.1124/jpet.105.090647. Epub 2005 Sep 20.


The effects of three volatile anesthetics (isoflurane, enflurane, and halothane) on basal release of glutamate and GABA from isolated rat cerebrocortical nerve terminals (synaptosomes) were compared using a dual isotope superfusion method. Concentration-dependent effects on basal release differed between anesthetics and transmitters. Over a range of clinical concentrations (0.5-2x minimum alveolar concentration), basal glutamate release was inhibited by all three anesthetics, whereas basal GABA release was enhanced (isoflurane) or unaffected (enflurane and halothane). These effects may represent a balance of stimulatory and inhibitory mechanisms between transmitters and anesthetics. There were no significant differences between anesthetic effects on basal release in the absence or presence of external Ca(2+), whereas intracellular Ca(2+) buffering limited volatile anesthetic inhibition of basal glutamate release. Although these results demonstrate fundamental differences in anesthetic effects on basal release between glutamatergic and GABAergic nerve terminals, all three volatile anesthetics at clinical concentrations consistently reduced the ratio of basal glutamate to GABA release. These actions may contribute to the net depression of glutamatergic excitation and potentiation of GABAergic inhibition characteristic of general anesthesia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Chelating Agents / pharmacology
  • Dose-Response Relationship, Drug
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Enflurane / pharmacology
  • Glutamic Acid / metabolism*
  • Halothane / pharmacology
  • In Vitro Techniques
  • Isoflurane / pharmacology
  • L-Lactate Dehydrogenase / metabolism
  • Male
  • Nerve Endings / drug effects
  • Nerve Endings / enzymology
  • Nerve Endings / metabolism*
  • Neurotransmitter Agents / metabolism
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / enzymology
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Aminobutyric Acid / metabolism*


  • Anesthetics, Inhalation
  • Chelating Agents
  • Neurotransmitter Agents
  • Glutamic Acid
  • Egtazic Acid
  • gamma-Aminobutyric Acid
  • Enflurane
  • Isoflurane
  • L-Lactate Dehydrogenase
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Halothane