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.
Department of Anesthesiology, University of Virginia, Charlottesville, Virginia 22908-0710, USA.
Soon-Ae
SA
Lee
Jun-Gwon
JG
Choi
Zhiyi
Z
Zuo
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D050580:Excitatory Amino Acid Transporter 3 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D008738:Methyl Ethers / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D051381:Rats; D000077149:Sevoflurane; D014982:Xenopus laevis; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D050580:Excitatory Amino Acid Transporter 3; D008738:Methyl Ethers; D018696:Neuroprotective Agents; C493398:Slc1a1 protein, rat; D000077149:Sevoflurane; D018698:Glutamic Acid; D020122:tert-Butylhydroperoxide; D000077335:Desflurane; D007530:Isoflurane; D003545:Cysteine