Midazolam and ketamine inhibit glutamate release via a cloned human brain glutamate transporter

In cerebral ischemia/anoxia, the glutamate transporter runs in reverse and releases glutamate into the extracellular space, causing irreversible neuronal damage. Intravenous anesthetics attenuate overall glutamate release and prevent neuronal injury during anoxia/ischemia, but their effect on the gl...

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Bibliographic Details
Published in:Canadian journal of anesthesia 2000-08, Vol.47 (8), p.800-806
Main Authors: SAKAI, F, AMAHA, K
Format: Article
Language:English
Subjects:
Amino Acid Transport System X-AG
Anesthetics - pharmacology
Anesthetics. Neuromuscular blocking agents
Animals
ATP-Binding Cassette Transporters - drug effects
ATP-Binding Cassette Transporters - physiology
Biological and medical sciences
Brain - drug effects
Brain - metabolism
CHO Cells
Cricetinae
Glutamic Acid - secretion
Humans
Ischemia
Ketamine - pharmacology
Medical sciences
Midazolam - pharmacology
Neurology
Neuropharmacology
Pharmacology. Drug treatments
Potassium Channels - drug effects
Recombinant Proteins - drug effects
Rodents
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Summary:In cerebral ischemia/anoxia, the glutamate transporter runs in reverse and releases glutamate into the extracellular space, causing irreversible neuronal damage. Intravenous anesthetics attenuate overall glutamate release and prevent neuronal injury during anoxia/ischemia, but their effect on the glutamate transporter is variable. A human glial glutamate transporter (hGLT-I) cDNA was isolated by screening a human cerebral cortical library. Cloned cDNA was transfected in Chinese hamster ovary cells. The effect of the intravenous anesthetics midazolam (0.3 to 30 microM), ketamine (10 to 100 microM), thiopental (30 to 300 microM), and propofol (3 to 30 microM) on reversed uptake of L-glutamate via hGLT-I was examined by whole-cell patch-clamp. Midazolam at a concentration 3 microM reduced outward currents arising from reversed L-glutamate uptake via hGLT-I in a concentration-dependent manner. While, ketamine at 100 microM attenuated the same outward currents, to 53.3+/-11.4% of those seen in controls without anesthetics (P
ISSN:0832-610X
1496-8975
DOI:10.1007/BF03019485