| Title | Volatile anesthetics attenuate oxidative stress-reduced activity of glutamate transporter type 3. | | Author(s) | Lee SA, Choi JG, Zuo Z | | Institution | Department of Anesthesiology, University of Virginia, Charlottesville, Virginia 22908-0710, USA. | | Source | Anesth Analg 2009 Nov; 109(5):1506-10. | | MeSH | Anesthetics, Inhalation
Animals
Cysteine
Dose-Response Relationship, Drug
Excitatory Amino Acid Transporter 3
Female
Glutamic Acid
Isoflurane
Kinetics
Membrane Potentials
Methyl Ethers
Neuroprotective Agents
Oxidative Stress
Rats
Xenopus laevis
tert-Butylhydroperoxide
| | 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. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19843789 |
|
