BINDING OF THE INWARD RECTIFIER K-2.3 TO PSD-95 IS REGULATED BY PROTEIN-KINASE-A PHOSPHORYLATION( CHANNEL KIR)

Dynamic regulation of ion channel interactions with the cytoskeleton m ediates aspects of synaptic plasticity, yet mechanisms for this proces s are largely unknown. Here, we report that two inwardly rectifying K channels, Kir 2.1 and 2.3, bind to PSD-95, a cytoskeletal protein of postsynaptic densities that clusters NMDA receptors and voltage-depend ent K+ channels. Kir 2.3 colocalizes with PSD-95 in neuronal populatio ns in forebrain, and a PSD-95/Kir 2.3 complex occurs in hippocampus. W ithin the C-terminal tail of Kir 2.3, a serine residue critical for in teraction with PSD-95, is also a substrate for phosphorylation by prot ein kinase A (PKA). Stimulation of PKA in intact cells causes rapid di ssociation of the channel from PSD-95. This work identifies a physiolo gical mechanism for regulating ion channel interactions with the posts ynaptic density.