AMPA-type receptors (AMPARs) are responsible for the fast component of glutamate mediated synaptic excitation in the CNS. Four receptor subunits exist (GluR1-4), with receptor heterogeneity being achieved through RNA editing, alternative splicing and heteromerization. Modulation of AMPARs underlies various forms of plasticity including long-term potentiation (LTP) and depression (LTD). GluR1-containing AMPARs are found in many cell populations that display LTP, including CA1 pyramidal cells of the hippocampus. Phosphorylation of two sites within the C-terminus of GluR1 can modulate either the single-channel conductance (Ser831; Derkach et al. 1999) or the peak channel open-probability (Ser845; Banke et al. 2000). Protein kinase A (PKA) and calcineurin, respectively, phosphorylate and dephosphorylate Ser845. Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates Ser831. We have now identified a phosphatase responsible for dephosphorylating this site, and have examined its effects on channel properties. We expressed recombinant AMPARs in tsA cells (a modified HEK293 cell line) transiently transfected with GluR1 and constitutively active forms of both CaMKII and Protein Phosphatase 1 (PP1). GluR1 responses were evoked by fast application of 10mM glutamate to outside-out patches. Unexpectedly, our initial experiments failed to demonstrate a potentiation of homomeric GluR1 AMPAR-currents following co-expression with CaMKII. However, following co-expression with PP1, the channel conductance decreased suggesting that an endogenous kinase (possibly a PKC isoform), maintains phosphorylation of GluR1 subunits in our conditions. GluR1 responses were analysed by non-stationary noise analysis, yielding a weighted-mean single-channel conductance of 23.1 ± 1.9pS (n = 7). This conductance was not significantly altered by CaMKII (25.8 ± 2.6pS; n = 6) but was decreased by PP1 (15.5 ± 1.2pS; n = 10, P <0.01 vs control and CaMKII). Our experiments have identified an experimental system in which GluR1 is constitutively phosphorylated. In these conditions the phosphatase PP1 is capable of down-regulating GluR1 responses by reducing channel conductance. Mice lacking PP1 show improved abilities in various tests of memory (Genoux et al. 2002). Thus, activation or inhibition of PP1 represents a potential method for induction of plasticity changes.