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

Soon Ae Lee, Jun Gwon Choi, Zhiyi Zuo

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 Vmax, but did not affect the Km, 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.

Original languageEnglish
Pages (from-to)1506-1510
Number of pages5
JournalAnesthesia and Analgesia
Volume109
Issue number5
DOIs
StatePublished - Nov 2009

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