Volatile anesthetic effects on glutamate versus GABA release from isolated rat cortical nerve terminals: 4-Aminopyridine-evoked release Academic Article uri icon

Overview

MeSH Major

  • 4-Aminopyridine
  • Anesthetics, Inhalation
  • Cerebral Cortex
  • Glutamic Acid
  • Nerve Endings
  • Potassium Channel Blockers
  • gamma-Aminobutyric Acid

abstract

  • Inhibition of glutamatergic excitatory neurotransmission and potentiation of GABA-mediated inhibitory transmission are possible mechanisms involved in general anesthesia. We compared the effects of three volatile anesthetics (isoflurane, enflurane, or halothane) on 4-aminopyridine (4AP)-evoked release of glutamate and GABA from isolated rat cerebrocortical nerve terminals (synaptosomes). Synaptosomes were prelabeled with l-[(3)H]glutamate and [(14)C]GABA, and release was evoked by superfusion with pulses of 1 mM 4AP in the absence or presence of 1.9 mM free Ca(2+). All three volatile anesthetics inhibited Ca(2+)-dependent glutamate and GABA release; IC(50) values for glutamate were comparable to clinical concentrations (1-1.6x MAC), whereas IC(50) values for GABA release exceeded clinical concentrations (>2.2x MAC). All three volatile anesthetics inhibited both Ca(2+)-independent and Ca(2+)-dependent 4AP-evoked glutamate release equipotently, whereas inhibition of Ca(2+)-dependent 4AP-evoked GABA release was less potent than inhibition of Ca(2+)-independent GABA release. Inhibition of Ca(2+)-independent 4AP-evoked glutamate release was more potent than that of GABA release for isoflurane and enflurane but equipotent for halothane. Tetrodotoxin inhibited both Ca(2+)-independent and Ca(2+)-dependent 4AP-evoked glutamate and GABA release equipotently, consistent with Na(+) channel involvement. In contrast to tetrodotoxin, volatile anesthetics exhibited selective effects on 4AP-evoked glutamate versus GABA release, consistent with distinct mechanisms of action. Preferential inhibition of Ca(2+)-dependent 4AP-evoked glutamate release versus GABA release supports the hypothesis that reduced excitatory neurotransmission relative to inhibitory neurotransmission contributes to volatile anesthetic actions.

publication date

  • January 2006

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1124/jpet.105.090662

PubMed ID

  • 16174800

Additional Document Info

start page

  • 216

end page

  • 23

volume

  • 316

number

  • 1