The effect of propofol on actin, ERK-1/2 and GABAA receptor content in neurones

• Published in: Acta anaesthesiologica Scandinavica 2007-10, Vol.51 (9), p.1184-1189
• Main Authors: Oscarsson, A., Juhas, M., Sjölander, A., Eintrei, C.
• Format: Article
• Language: English
• Subjects: Actin; Actins - drug effects; aminobutyric acid receptor; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthetics, Intravenous - pharmacology; Animals; Bicuculline - pharmacology; Biological and medical sciences; extracellular signal-regulated kinase-1/2 (ERK-1/2); Extracellular Signal-Regulated MAP Kinases - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; GABA Antagonists - pharmacology; Medical sciences; MEDICIN; MEDICINE; mitogen-activated protein kinase (MAPK); Neurons - chemistry; Neurons - drug effects; Propofol; Propofol - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - drug effects; Receptors, GABA-A - metabolism; γ-aminobutyric acid receptor
• ISSN: 0001-5172; 1399-6576; 1399-6576
• DOI: 10.1111/j.1399-6576.2007.01388.x

Aim:  Interaction with the γ‐aminobutyric acid receptor (GABAAR) 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 GABAAR 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 GABAAβ2‐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 GABAAβ2‐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 GABAAβ2‐subunit content, and ERK‐1/2 phosphorylation. Conclusion:  We believe that propofol triggers a dose‐dependent internalization of the GABAAβ2‐subunit. The increase in internal GABAAβ2‐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 GABAAβ2‐subunit.