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Anesth Analg 1999;89:1546
© 1999 International Anesthesia Research Society

GENERAL ARTICLES

The Effects of Hypothermia on a Cloned Human Brain Glutamate Transporter (hGLT-1) Expressed in Chinese Hamster Ovary Cells: -[3H]L-Glutamate Uptake Study

Fumio Sakai, MD, PhD, and Keisuke Amaha, MD, PhD

Department of Anesthesiology and Critical Care Medicine, Tokyo Medical and Dental University, Tokyo, Japan

Address correspondence and reprint requests to Fumio Sakai, MD, PhD, Department of Anesthesiology and Critical Care Medicine, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo, 113-8519 Japan.

Hypothermia provides neuroprotection that inhibits increases in extracellular glutamate concentration during ischemia; however, the effect of hypothermia on the glutamate transporter is uncertain. A human glial glutamate transporter (hGLT-1) cDNA, isolated by screening a cDNA, library was cloned and stably transfected into Chinese hamster ovary cells. We assessed the effects of temperature on transporter activity in [3H]L-glutamate flux experiments at 23, 32, and 37°C. Hypothermia of 23°C and 32°C decreased [3H]L-glutamate uptake at 60 min, to 76.7% ± 7.3% (P < 0.05, n = 5) and 70.7% ± 7.5% (P < 0.05, n = 5) of uptake at 37°C, respectively. Reversed uptake of preloaded [3H]L-glutamate via hGLT-1 was not observed at any temperature. The specific uptakes (Q10 values) for 37°C to 32°C and 32°C to 23°C at 30 min were 3.48 and 2.37, whereas they were 2.17 and 0.91, respectively, for 60 min. These changes suggest that hypothermia attenuates uptake of extracellular glutamate via hGLT-1 in a temperature- and time-dependent manner.

Implications: Under certain pathologic conditions, including cerebral ischemia and traumatic brain injury, glutamate neurotoxicity may initially be propagated by hypothermia due to relative failure of glutamate uptake via Human Glial Glutamate Transporter before a subsequent recovery of uptake.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 1999 by the International Anesthesia Research Society.