Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase

• Type of Material: Article
• Authors: T.G. Banke, Emory University; D. Bowie, Emory University; H.K. Lee, Johns Hopkins University; R.L. Huganir, Johns Hopkins University; A. Schousboe, Royal Danish School of Pharmacy; Stephen Traynelis, Emory University
• Language: English
• Date: 2000-01-01
• Publisher: Society for Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: © 1999 Society for Neuroscience. CC BY 4.0
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.20-01-00089.2000
• Title of Journal or Parent Work: Journal of Neuroscience
• ISSN: 1529-2401
• Volume: 20
• Issue: 1
• Start Page: 89
• End Page: 102
• Grant/Funding Information: This work was generously supported by the Danish State Biotechnology Program (T.G.B.), the Howard Hughes Medical Institute (R.L.H.), the Danish Medical Research Council (A.S.), and the National Institute of Neurological Diseases and Stroke (S.F.T.).
• Keywords: Neurosciences; LTD; LONG-TERM DEPRESSION; PKA; KAINATE RECEPTORS; glutamate; Life Sciences & Biomedicine; Neurosciences & Neurology; SINGLE-CHANNEL PROPERTIES; AMPA receptors; CA3 PYRAMIDAL CELLS; EXCITATORY AMINO-ACIDS; SYNAPTIC TRANSMISSION; RAT HIPPOCAMPAL SLICES; AVIAN COCHLEAR NUCLEUS; Science & Technology; GluR1; calcineurin; GLUTAMATE-OPERATED CHANNELS; CYCLIC-AMP; open probability
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

Abstract

Modulation of postsynaptic AMPA receptors in the brain by phosphorylation may play a role in the expression of synaptic plasticity at central excitatory synapses. It is known from biochemical studies that GluR1 AMPA receptor subunits can be phosphorylated within their C terminal by cAMP- dependent protein kinase A (PKA), which is colocalized with the phosphatase calcineurin (i.e., phosphatase 2B). We have examined the effect of PKA and calcineurin on the time course, peak open probability (P(O,PEAK)), and single-channel properties of glutamate-evoked responses for neuronal AMPA receptors and homomeric GluR1 (flip) receptors recorded in outside-out patches. Inclusion of purified catalytic subunit Cα-PKA in the pipette solution increased neuronal AMPA receptor P(O,PEAK) (0.92) compared with recordings made with calcineurin included in the pipette (P(O,PEAK) 0.39). Similarly, Cα-PKA increased P(O,PEAK) for recombinant GluR1 receptors (0.78) compared with patches excised from cells cotransfected with a cDNA encoding the PKA peptide inhibitor PKI (P(O,PEAK) 0.50) or patches with calcineurin included in the pipette (P(O,PEAK) 0.42). Neither PKA nor calcineurin altered the amplitude of single-channel subconductance levels, weighted mean unitary current, mean channel open period, burst length, or macroscopic response waveform for recombinant GluR1 receptors. Substitution of an amino acid at the PKA phosphorylation site (S845A) on GluR1 eliminated the PKA-induced increase in P(O,PEAK), whereas the mutation of a Ca2+, calmodulin-dependent kinase II and PKC phosphorylation site (S831A) was without effect. These results suggest that AMPA receptor peak response open probability can be increased by PKA through phosphorylation of GluR1 Ser845.