Modulation of AMPA receptor GluR1 subunit phosphorylation in neurons by the intravenous anaesthetic propofol

Abstract

Background. The ionotropic glutamate receptor is a potential molecular site in the central nervous system that general anaesthetics may interact with to produce some of their biological actions. Protein phosphorylation has been well documented to occur in the intracellular C-terminal domain of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors, which represents a pivotal mechanism for the post-translational modulation of AMPA receptor functions. In this study, we investigated a possible influence of an i.v. anaesthetic agent propofol on the phosphorylation of AMPA receptor GluR1 subunits in cultured neurons. Methods. The effect of propofol on phosphorylation of GluR1 subunits at serine 831 and 845 was assayed in cultured rat striatal and cortical neurons by western blot with phospho- and site-specific antibodies. Results. Propofol consistently elevated phosphorylation of GluR1 subunits at the C-terminal serine 845 site in both striatal and cortical neurons. The elevation in phosphorylation was concentration-dependent and started at a low concentration (3 μM). This increase in serine 845 phosphorylation was rapid and sustained during the entire course of propofol exposure. In contrast to serine 845, phosphorylation of GluR1 at serine 831 was not altered by propofol in striatal and cortical neurons. Total GluR1 abundance remained unchanged in response to propofol incubation. Conclusions. These data indicate that propofol possesses the ability to upregulate AMPA receptor GluR1 subunit phosphorylation at a specific serine 845 site in neurons and provide evidence supporting the AMPA receptor as a molecular target for general anaesthetics. © The Board of Management and Trustees of the British Journal of Anaesthesia 2008. All rights reserved.