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Anesth Analg 2000;91:353-357
© 2000 International Anesthesia Research Society

NEUROSURGICAL ANESTHESIA

A Correlation Between Dexmedetomidine-Induced Biphasic Increases in Free Cytosolic Calcium Concentration and Energy Metabolism in Astrocytes

Ye Chen, MD, PhD, Zhong Zhao, MSc, William E. Code, MD, and Leif Hertz, MD, DSc

Departments of Pharmacology and Anesthesia, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

Address correspondence to Ye Chen, MD, PhD, Stroke Branch, NINDS/NIH, 36 Convent Dr., MSC 4128, Bethesda, MD 20892-4128. Address e-mail to chenye{at}codon.nih.gov

The {alpha}2-adrenergic agonist, dexmedetomidine, increases free cytosolic calcium concentration ([Ca2+]i) in astrocytes, but not in neurons. The present study was performed to characterize the origin of the increased Ca2+ in mouse astrocytes cultured from the cerebral cortex, the dose dependence of the effect, and its functional consequences. The increase in [Ca2+]i was independent of extracellular Ca2+, but was inhibited by dantrolene, showing that it is derived from intracellular stores; two peaks in [Ca2+]i were demonstrated—one around 100 nM dexmedetomidine and the other in the low micromolar range. A similar dose dependence was found for pyruvate dehydrogenation, the initial metabolic reaction of oxidative degradation of pyruvate, suggesting that the these events are interrelated. The {alpha}2-adrenergic antagonist, yohimbine, abolished the metabolic stimulation at both peaks. However, whereas the increase in [Ca2+] i at 100 nM is abolished by yohimbine, increase in the micromolar range was partly inhibited by yohimbine and partly by idazoxan, an inhibitor at the imidazoline-preferring site. The stimulation of energy metabolism in cerebrocortical astrocytes may explain the repeated finding that dexmedetomidine does not decrease oxidative metabolism in the brain in vivo. The functional importance of the additional imidazoline receptor-mediated increase in [Ca2+]i at large dexmedetomidine concentrations is unknown.

Implications: Cytosolic calcium concentration and metabolism were measured in cultured astrocytes, the predominant glial cells. The results suggest that dexmedetomidine may owe its anesthetic effects to a Ca2+-dependent increase in astrocytic energy metabolism, allowing these cells to more effectively remove extracellular glutamate and potassium ions, and thus, decreasing neuronal excitability.






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 © 2000 by the International Anesthesia Research Society.