Hostname: page-component-848d4c4894-nmvwc Total loading time: 0 Render date: 2024-06-22T22:46:35.713Z Has data issue: false hasContentIssue false
  • English
  • Français

Effects of propofol on N-methyl-d-aspartate receptor-mediated calcium increase in cultured rat cerebrocortical neurons

Published online by Cambridge University Press:  02 June 2005

C. Grasshoff  and
T. Gillessen
C. Grasshoff
Affiliation:
Eberhard-Karls-University, Department of Anaesthesiology and Intensive Care, Tuebingen, Germany GAF Pharmacological Institute, Muenchen, Germany
T. Gillessen
Affiliation:
GAF Pharmacological Institute, Muenchen, Germany Present address: Dachau General Hospital, Department of Neurology, Krankenhausstrasse 15, 85221 Dachau, Germany.
Get access

Extract

Summary

Background and 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 μmol) on intracellular calcium increase induced by 300 μmol 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 μmol 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 μmol. The overall effect was small, since even high concentrations of propofol (100 μmol) 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.

Keywords

ANAESTHETICS, INTRAVENOUS, propofolRECEPTOR STIMULATION, RECEPTORS N-METHYL-d-ASPARTATENEURONS, intracellular calcium
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 6 , June 2005 , pp. 467 - 470
Copyright
© 2005 European Society of Anaesthesiology

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Kochs E, Hoffman WE, Werner C, Thomas C, Albrecht RF, Schulte am EJ. The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats. Anesthesiology 1992; 76: 245–252.Google Scholar
Young Y, Menon DK, Tisavipat N, Matta BF, Jones JG. Propofol neuroprotection in a rat model of ischaemia reperfusion injury. Eur J Anaesthesiol 1997; 14: 320–326.Google Scholar
Ito H, Watanabe Y, Isshiki A, Uchino H. Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand 1999; 43: 153–162.Google Scholar
Murphy PG, Myers DS, Davies MJ, Webster NR, Jones JG. The antioxidant potential of propofol (2,6-diisopropylphenol). Br J Anaesth 1992; 68: 613–618.Google Scholar
Sagara Y, Hendler S, Khoh RS, et al. Propofol hemisuccinate protects neuronal cells from oxidative injury. J Neurochem 1999; 73: 2524–2530.Google Scholar
Grasshoff C, Gillessen T. The effect of propofol on increased superoxide concentration in cultured rat cerebrocortical neurons after stimulation of N-methyl-d-aspartate receptors. Anesth Analg 2002; 95: 920–922.Google Scholar
Nicholls DG, Budd SL. Mitochondria and neuronal glutamate excitotoxicity. Biochim Biophys Acta 1998; 1366: 97–112.Google Scholar
Gillessen T, Grasshoff C, Szinicz L. Mitochondrial permeability transition can be directly monitored in living neurons. Biomed Pharmacother 2002; 56: 186–193.Google Scholar
Lipowsky R, Gillessen T, Alzheimer C. Dendritic Na+ channels amplify EPSPs in hippocampal CA1 pyramidal cells. J Neurophysiol 1996; 76: 2181–2191.Google Scholar
de Lima AD, Opitz T, Voigt T. Irreversible loss of a subpopulation of cortical interneurons in the absence of glutamatergic network activity. Eur J Neurosci 2004; 19: 2931–2943.Google Scholar
Gillessen T, Alzheimer C. Amplification of EPSPs by low Ni(2+)- and amiloride-sensitive Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. J Neurophysiol 1997; 77: 1639–1643.Google Scholar
Choi DW, Maulucci GM, Krieglstein AR. Glutamate neurotoxicity in cortical cell culture. J Neurosci 1987; 7: 357–368.Google Scholar
Amorim P, Chambers G, Cottrell J, Kass IS. Propofol reduces neuronal transmission damage and attenuates the changes in calcium, potassium, and sodium during hyperthermic anoxia in the rat hippocampal slice. Anesthesiology 1995; 83: 1254–1265.Google Scholar
Hans P, Bonhomme V, Collette J, Albert A, Moonen G. Propofol protects cultured rat hippocampal neurons against N-methyl-d-aspartate receptor-mediated glutamate toxicity. J Neurosurg Anesthesiol 1994; 6: 249–253.Google Scholar
Rehberg B, Duch DS. Suppression of central nervous system sodium channels by propofol. Anesthesiology 1999; 91: 512–520.Google Scholar
Tonner PH, Poppers DM, Miller KW. The general anesthetic potency of propofol and its dependence on hydrostatic pressure. Anesthesiology 1992; 77: 926–931.Google Scholar
Franks NP, Lieb WR. Molecular and cellular mechanisms of general anaesthesia. Nature 1994; 367: 607–614.Google Scholar
Smith C, McEwan AI, Jhaveri R, et al. The interaction of fentanyl on the Cp50 of propofol for loss of consciousness and skin incision. Anesthesiology 1994; 81: 820–828.Google Scholar