Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation

Neuron. 1996 Oct;17(4):759-67. doi: 10.1016/s0896-6273(00)80207-x.


Dynamic regulation of ion channel interactions with the cytoskeleton mediates aspects of synaptic plasticity, yet mechanisms for this process 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-dependent K+ channels. Kir 2.3 colocalizes with PSD-95 in neuronal populations in forebrain, and a PSD-95/Kir 2.3 complex occurs in hippocampus. Within the C-terminal tail of Kir 2.3, a serine residue critical for interaction with PSD-95, is also a substrate for phosphorylation by protein kinase A (PKA). Stimulation of PKA in intact cells causes rapid dissociation of the channel from PSD-95. This work identifies a physiological mechanism for regulating ion channel interactions with the postsynaptic density.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Blotting, Western
  • Calcimycin / pharmacology
  • Cell Line
  • Colforsin / pharmacology
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Humans
  • Kidney
  • Mammals
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Phosphorylation
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection


  • KCNJ4 protein, human
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Proto-Oncogene Proteins c-myc
  • Recombinant Proteins
  • postsynaptic density proteins
  • Colforsin
  • Calcimycin
  • Cyclic AMP-Dependent Protein Kinases
  • Tetradecanoylphorbol Acetate