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

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.