Int J Physiol Pathophysiol Pharmacol 2010;2(1):47-56.
Original Article Reciprocal and activity-dependent regulation of surface AMPA and NMDA receptors in cultured neurons
Guo Hua Li, Michael F. Jackson, Beverley A. Orser, John F. MacDonald
Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Robarts Research Institute, Department of Physiology and Pharmacology, Department of Anatomy and Cell biology, University of Western Ontario, London, Ontario; Departments of Anesthesia, Department of Physiology, University of Toronto, Toronto, Ontario, Canada
Received December 7, 2009; accepted December 20, 2009; available online January 1, 2010
Abstract: Activation of NMDA receptors (NMDARs) can modulate excitatory synaptic transmission in the central nervous system by dynamically altering the number of synaptic AMPA receptors (AMPARs). The surface expression of NMDARs themselves is also subject to modulation in an activity-dependent manner. In addition to NMDAR-induced changes in AMPAR expression, AMPARs have also been found to regulate their own surface expression, independently of NMDARs. However, whether or not AMPARs and NMDARs might reciprocally regulate their surface expression has not previously been systematically explored. We utilized surface biotinylation assays and stimulation protocols intended to selectively stimulate various glutamate receptor subpopulations (e.g. AMPARs vs NMDARs; synaptic vs extrasynaptic). We reveal that activation of synaptic NMDA receptors increases the surface expression of both NMDAR and AMPAR subunits, while activation of extrasynaptic NMDAR produces the opposite effect. Surprisingly, we find that selective activation of AMPARs reduces the surface expression of not only AMPARs but also of NMDARs. These results suggest that both AMPARs and NMDARs at synaptic sites are subject to modulation by multiple signalling pathways in an activity-dependent way.(IJPPP912001).