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Characterisation of the signal transduction cascade caused by propofol in rat neurons: From the GABAA receptor to the cytoskeleton
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Anesthesiology .
Department of Anaesthesiology Linköping University.
Department of Anaesthesiology Linköping University.
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2008 (English)In: Journal of Physiology and Pharmacology, ISSN 0867-5910, E-ISSN 1899-1505, Vol. 59, no 3, 617-632 p.Article in journal (Refereed) Published
Abstract [en]

The anaesthetic propofol interacts with the GABAA receptor, but its cellular signalling pathways are not fully understood. Propofol causes reorganisation of the actin cytoskeleton into ring structures in neurons. Is this reorganisation a specific effect of propofol as apposed to GABA, and which cellular pathways are involved? We used fluorescence-marked actin in cultured rat neurons to evaluate the percentage of actin rings caused by propofol or GABA in combination with rho, rho kinase (ROK), PI3-kinase or tyrosine kinase inhibitors, with or without the presence of extracellular calcium. Confocal microscopy was performed on propofol-stimulated cells and changes in actin between cellular compartments were studied with Western blot. Propofol (3 μg·ml-1), but not GABA (5 μM), caused transcellular actin ring formation, that was dependent on influx of extracellular calcium and blocked by rho, ROK, PI3-kinase or tyrosine kinase inhibitors. Propofol uses rho/ROK to translocate actin from the cytoskeleton to the membrane and its actin ring formation is dependent on an interaction site close to the GABA site on the GABAA receptor. GABA does not cause actin rings, implying that this is a specific effect of propofol.

Place, publisher, year, edition, pages
2008. Vol. 59, no 3, 617-632 p.
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-43536Local ID: 74109OAI: oai:DiVA.org:liu-43536DiVA: diva2:264395
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13

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Björnström, KarinTurina, DeanWijkman, MagnusLindroth, MargarethaEintrei, Christina

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Björnström, KarinTurina, DeanWijkman, MagnusLindroth, MargarethaEintrei, Christina
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Faculty of Health SciencesAnaesthesiologyDepartment of Intensive Care UHLAnesthesiology Internal Medicine Medical Microbiology
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