Effects of propofol on N-methyl-D-aspartate receptor-mediated calcium increase in cultured rat cerebrocortical neurons.
OBJECTIVE
The intravenous anaesthetic propofol has been reported to exert neuroprotective actions by several mechanisms. This study has been designed to investigate the effects of propofol on intracellular calcium increase in cultured cerebrocortical neurons after exposure to pathological concentrations of N-methyl-D-aspartate (NMDA) mediated by potential direct interactions of propofol with NMDA receptors.


METHODS
The effects of propofol (0.1-100 micromol) on intracellular calcium increase induced by 300 micromol NMDA (180 s) were measured in cultured cerebrocortical neurons using the calcium-sensitive fluorochrome calcium green-5N-acetoxymethylester with confocal laser scanning microscopy.


RESULTS
The intraneuronal calcium increase after exposure to 300 micromol NMDA depended on extracellular calcium concentration. Propofol reduced the increase of NMDA receptor-induced intraneuronal calcium concentration dependently with a threshold concentration for a significant effect of 10 micromol. The overall effect was small, since even high concentrations of propofol (100 micromol) diminished intraneuronal calcium rise by only 50%.


CONCLUSIONS
The threshold concentration for significant effects of propofol on the NMDA-induced increase of intraneuronal calcium turned out to be in the upper limit of propofol concentrations that are considered to be clinically relevant. However, in the presence of high propofol concentrations, inhibition of NMDA receptor-mediated calcium increase might contribute to neuroprotective effects observed with propofol.
Grasshoff
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Eberhard-Karls-University, Department of Anaesthesiology and Intensive Care, Tuebingen, Germany. christian.grasshoff@uni-tuebingen.de
Gillessen
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T
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes; D018613:Microscopy, Confocal; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009930:Organic Chemicals; D011247:Pregnancy; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D018690:Excitatory Amino Acid Agonists; D005456:Fluorescent Dyes; D009930:Organic Chemicals; D016194:Receptors, N-Methyl-D-Aspartate; C071336:calcium green; D016202:N-Methylaspartate; D002118:Calcium; D015742:Propofol