The effect of propofol on actin, ERK-1/2 and GABAA receptor content in neurones
2007 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, Vol. 51, no 9, 1184-1189 p.Article in journal (Refereed) Published
Aim: Interaction with the ?-aminobutyric acid receptor (GABA AR) complex is recognized as an important component of the mechanism of many anaesthetic agents, including propofol. The aims of this study were to investigate the effect of propofol on GABAAR, to determine whether exposure of neurones to propofol influences the localization of GABA AR within the cell and to look for cytoskeletal changes that may be connected with activation, such as the mitogen-activated protein kinase (MAPK) pathway. Methods: Primary cortical cell cultures from rat, with and without pre-incubation with the GABAAR antagonist bicuculline, were exposed to propofol. The cells were lysed and separated into membrane and cytosolic fractions. Immunoblot analyses of filamentous actin (F-actin), the GABA A ß2-subunit receptor and extracellular signal-regulated kinase-1/2 (ERK-1/2) were performed. Results: Propofol triggers an increase in GABAAR, actin content and ERK-1/2 phosphorylation in the cytosolic fraction. In the membrane fraction, there is a decrease in GABAA ß2-subunit content and an increase in both actin content and ERK-1/2 phosphorylation. The GABAAR antagonist bicuculline blocks the propofol-induced changes in F-actin, ERK and GABA A ß2-subunit content, and ERK-1/2 phosphorylation. Conclusion: We believe that propofol triggers a dose-dependent internalization of the GABAA ß2-subunit. The increase in internal GABAA ß2-subunit content exhibits a close relationship to actin polymerization and to an increase in ERK-1/2 activation. Actin contributes to the internalization sequestering of the GABAA ß2-subunit. © 2007 Acta Anaesthesiol Scand.
Place, publisher, year, edition, pages
2007. Vol. 51, no 9, 1184-1189 p.
?-aminobutyric acid receptor, Actin, Extracellular signal-regulated kinase-1/2 (ERK-1/2), Mitogen-activated protein kinase (MAPK), Propofol
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-48577DOI: 10.1111/j.1399-6576.2007.01388.xOAI: oai:DiVA.org:liu-48577DiVA: diva2:269473