Control of GluR1 AMPA Receptor Function by cAMP-Dependent Protein Kinase

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 bio-chemical 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 phospha-tase calcineurin (i.e., phosphatase 2B). We have examined the effect of PKA and calcineurin on the time course, peak open probability (PO,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 Ca-PKA in the pipette solution in-creased neuronal AMPA receptor PO,PEAK (0.92) compared with recordings made with calcineurin included in the pipette (PO,PEAK 0.39). Similarly, Ca-PKA increased PO,PEAK for recom