PT  - JOURNAL ARTICLE
AU  - Greg Broutman
AU  - Michel Baudry
TI  - Involvement of the Secretory Pathway for AMPA Receptors in NMDA-Induced Potentiation in Hippocampus
AID  - 10.1523/JNEUROSCI.21-01-00027.2001
DP  - 2001 Jan 01
TA  - The Journal of Neuroscience
PG  - 27--34
VI  - 21
IP  - 1
4099  - http://www.jneurosci.org/content/21/1/27.short
4100  - http://www.jneurosci.org/content/21/1/27.full
SO  - J. Neurosci.2001 Jan 01; 21
AB  - A chemical form of synaptic potentiation was produced with a brief bath application of NMDA to rat hippocampal slices. Two methods were used to assess changes in membrane-bound AMPA receptors. Traditional subcellular fractionation was used to isolate synaptic membranes; alternatively, membrane receptors were cross-linked with the membrane-impermeable reagent bis(sulfosuccinimidyl) suberate, and levels of nonmembrane receptors were determined. In both cases, Western blots were used to determine the content of receptor subunits in various subcellular fractions. NMDA-induced potentiation was associated with increased levels of glutamate receptor 1 (GluR1) and GluR2/3 subunits of AMPA receptors in synaptic membrane preparations, whereas no change was observed in whole homogenates. Both KN-62, an inhibitor of calcium/calmodulin kinase, and calpain inhibitor III, a calpain inhibitor, inhibited NMDA-induced potentiation and changes in GluR1 and GluR2/3 subunits of AMPA receptors. Brefeldin A (BFA) inhibits protein trafficking between the Golgi apparatus and cell membranes. Pretreatment of hippocampal slices with BFA significantly decreased NMDA-induced potentiation and completely prevented an NMDA-induced increase in GluR1 levels in membrane fractions. Thus, the levels of GluR1 and GluR2/3 subunits of AMPA receptors are rapidly upregulated in synaptic membranes under conditions associated with potentiation of synaptic responses, and this upregulation requires a functional secretory pathway.