Effects of isoflurane and propofol on glutamate and GABA transporters in isolated cortical nerve terminals. Academic Article uri icon

Overview

abstract

  • BACKGROUND: Depression of glutamate-mediated excitatory transmission and potentiation of gamma-aminobutyric acid (GABA)-mediated inhibitory transmission appear to be primary mechanisms by which general anesthetics produce anesthesia. Since effects on transmitter transport have been implicated in anesthetic actions, the authors examined the sensitivity of presynaptic glutamate and GABA transporters to the effects of a representative volatile (isoflurane) and a representative intravenous (propofol) anesthetic. METHODS: A dual-isotope (l-[3H]glutamate and [14C]GABA) approach allowed simultaneous comparisons of anesthetic effects on three independent assays of glutamate and GABA transporters in adult rat cerebral cortex: transmitter uptake into isolated nerve terminals (synaptosomes), transmitter binding to lysed and washed synaptosomes (synaptic membranes), and carrier-mediated release (reverse transport) of transmitter from preloaded synaptosomes using a modified superfusion system. RESULTS: Isoflurane produced small but statistically significant inhibition of l-[3H]glutamate and [14C]GABA uptake, while propofol had no effect. Inhibition of uptake by isoflurane was noncompetitive, an outcome that was mimicked by indirectly affecting transporter function through synaptosomal depolarization. Neither isoflurane nor propofol affected l-[3H]glutamate or [14C]GABA binding to synaptic membranes or Ca(2+)-independent carrier-mediated l-[3H]glutamate or [14C]GABA release (reverse transport). CONCLUSIONS: These findings suggest that isoflurane and propofol at clinical concentrations do not affect excitatory glutamatergic transmission or inhibitory GABAergic transmission directly effects on their presynaptic neuronal transporters.

publication date

  • February 1, 2003

Research

keywords

  • Amino Acid Transport System X-AG
  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Carrier Proteins
  • Cerebral Cortex
  • Isoflurane
  • Membrane Proteins
  • Membrane Transport Proteins
  • Nerve Endings
  • Organic Anion Transporters
  • Propofol

Identity

Scopus Document Identifier

  • 0037317564

PubMed ID

  • 12552195

Additional Document Info

volume

  • 98

issue

  • 2