Research article summary (published 30 Oct 2009):

Volatile anesthetics attenuate oxidative stress-reduced activity of glutamate transporter type 3.

Full Abstract

BACKGROUND: Volatile anesthetics enhance the activity of glutamate transporter Type 3 (also called excitatory amino acid transporter Type 3, EAAT3), the major neuronal EAAT. In addition to glutamate, EAAT3 can also uptake L-cysteine, the rate-limiting substrate for the synthesis of glutathione. Our previous study showed that oxidative stress inhibited glutamate-induced EAAT3 activity. We determined whether oxidative stress would reduce L-cysteine-induced EAAT3 activity and whether this reduction would be attenuated by volatile anesthetics. METHODS: Rat EAAT3 was expressed in Xenopus oocytes. L-glutamate- and L-cysteine-induced membrane currents were recorded using the 2-electrode voltage clamp technique. The peak current was quantified to reflect the amount of transported substrates because transport of substrates via EAATs is electrogenic. RESULTS: Exposure of oocytes to 5 mM tert-butyl hydroperoxide, an organic oxidant, for 10 min reduced the V(max), but did not affect the K(m), of EAAT3 for L-cysteine. The volatile anesthetics isoflurane, sevoflurane, and desflurane at concentrations from 1% to 3% attenuated the tert-butyl hydroperoxide-reduced EAAT3 activity for L-glutamate and L-cysteine. CONCLUSIONS: Our results suggest that volatile anesthetics preserve EAAT3 function to transport L-glutamate and L-cysteine under oxidative stress, which may be a mechanism for the neuroprotective effects of volatile anesthetics.

Author information

Author/s: Lee, Soon-Ae (SA); Choi, Jun-Gwon (JG); Zuo, Zhiyi (Z);

Affiliation: Department of Anesthesiology, University of Virginia, Charlottesville, Virginia 22908-0710, USA.

Grants: R01 GM065211 (Agency:NIGMS NIH HHS) ; R01 NS045983 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Anesthesia and analgesia (Anesth Analg), published in United States. (Language: eng)

Reference: 2009-Nov; vol 109 (issue 5) : pp 1506-10

Dates: Created 2009/10/21; Completed 2009/11/05; Revised 2009/11/06;

PMID: 19843789, status: MEDLINE (last retrieval date: 11/9/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Anesthetics, Inhalation - pharmacology Animals Cysteine - metabolism Dose-Response Relationship, Drug Excitatory Amino Acid Transporter 3 - drug effects; genetics; metabolism Female Glutamic Acid - metabolism Isoflurane - analogs & derivatives; pharmacology

Kinetics Membrane Potentials Methyl Ethers - pharmacology Neuroprotective Agents - pharmacology Oxidative Stress Rats Xenopus laevis tert-Butylhydroperoxide - pharmacology

Associated Chemicals: Anesthetics, Inhalation (0) ; Excitatory Amino Acid Transporter 3 (0) ; Methyl Ethers (0) ; Neuroprotective Agents (0) ; Slc1a1 protein, rat (0) ; Isoflurane (26675-46-7) ; sevoflurane (28523-86-6) ; Cysteine (52-90-4) ; Glutamic Acid (56-86-0) ; desflurane (57041-67-5) ; tert-Butylhydroperoxide (75-91-2)

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