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ANESTHETIC PHARMACOLOGY

Volatile Anesthetics Attenuate Oxidative Stress-Reduced Activity of Glutamate Transporter Type 3

Soon-Ae Lee, MD, PhD^*, Jun-Gwon Choi, MD, and Zhiyi Zuo, MD, PhD^*

From the *Department of Anesthesiology, University of Virginia, Charlottesville, Virginia; Department of Anesthesiology and Pain Medicine, Center for Liver Cancer, National Cancer Center; and Department of Anesthesia and Pain Medicine, Ilsan Dongguk University Hospital, Goyang-si, Gyeonggi-Do, Republic of Korea.

Address correspondence and reprint requests to Zhiyi Zuo, MD, PhD, Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710. Address e-mail to zz3c{at}virginia.edu.

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.