Ketamine stereoselectively inhibits spontaneous Ca2+- oscillations in cultured hippocampal neurons

Sinner, B., Friedrich, O., Zink, W., Martin, E., Fink, R. H. A. and Graf, B. M. (2005) Ketamine stereoselectively inhibits spontaneous Ca2+- oscillations in cultured hippocampal neurons. Anesthesia and Analgesia, 100 6: 1660-1666. doi:10.1213/01.ANE.0000150946.18875.48


Author Sinner, B.
Friedrich, O.
Zink, W.
Martin, E.
Fink, R. H. A.
Graf, B. M.
Title Ketamine stereoselectively inhibits spontaneous Ca2+- oscillations in cultured hippocampal neurons
Formatted title
Ketamine stereoselectively inhibits spontaneous Ca2+- oscillations in cultured hippocampal neurons
Journal name Anesthesia and Analgesia   Check publisher's open access policy
ISSN 0003-2999
1526-7598
Publication date 2005-06-01
Sub-type Article (original research)
DOI 10.1213/01.ANE.0000150946.18875.48
Volume 100
Issue 6
Start page 1660
End page 1666
Total pages 7
Editor Ronald D. Miller
Place of publication Baltimore, MD, U.S.A.
Publisher Lippincott Williams & Wilkins
Language eng
Subject 1103 Clinical Sciences
Formatted abstract
Spontaneous Ca2+-oscillations are a result of periodic increases and decreases of cytosolic Ca2+. In neurons, they are thought to possess integrative properties because amplitude and frequency influence axon outgrowth, neuronal growth cone migration, and long distant wiring within the developing cortex. Ketamine stereoisomers differ in their affinities for the N-methyl-D-aspartic acid receptor and analgesic and anesthetic effects. Using a dual-excitation Ca2+ ratiometric fluorescence technique with the Ca2+-sensitive dye fura-2 AM, we detected spontaneous Ca 2+-oscillations in neurons of hippocampal cell cultures. Spontaneous Ca2+-oscillations development is dependent on external Ca 2+, and their amplitude and frequency increased in Mg 2+-free solution. Ca2+-oscillations are glutamate dependent because blocking of the N-methyl-D-aspartic acid, α-amino-3- hydroxy-5-methyl-4-isoxazolepropiorvic, or kainate receptor resulted in a complete disruption of the oscillations. The ketamine stereoisomers dose-dependently and reversibly suppressed the amplitude and frequency of the spontaneous Ca2+-oscillations. This effect was highly stereoselective with the S(+) isomer being nearly four times more potent than the R(-) enantiomer. These results correlate well with the clinical anesthetic and analgesic potency of the stereoisomers and therefore our experimental approach might represent a model system to study mechanisms of anesthetic action on Ca2+-dependent integration of neuronal information.
©2005 by the International Anesthesia Research Society.
Keyword Anesthetics
Dissociative
Calcium channels
Calcium signaling
Cultured cells
Drug dose-response relationship
Excitatory amino acid antagonists
Fluorometry
Hippocampus
Ketamine
Stereoisomerism
GABA-A
Glutamate receptors
Membrane potentials
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 11 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 06 Apr 2010, 22:48:54 EST by June Temby on behalf of Faculty of Science