Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation

Neuron. 1995 Nov;15(5):1133-43. doi: 10.1016/0896-6273(95)90101-9.


Activation of G protein-gated K+ channels by G protein-coupled receptors contributes to parasympathetic regulation of heart rate in the atrium and inhibitory postsynaptic potentials in the peripheral and central nervous system. Having found that G beta gamma activates the cloned GIRK1 channel, we now report evidence for direct binding of G beta gamma to both the N-terminal hydrophilic domain and amino acids 273-462 of the C-terminal domain of GIRK1. These direct interactions are physiologically important because synthetic peptides derived from either domain reduce the G beta gamma binding as well as the G beta gamma activation of the channel. Moreover, the N-terminal domain may also bind trimeric G alpha beta gamma, raising the possibility that physical association of G protein-coupled receptors, G proteins, and K+ channels partially accounts for their compartmentalization and hence rapid and specific channel activation by receptors.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Baculoviridae / genetics
  • Binding Sites
  • Blotting, Western
  • Chemical Precipitation
  • Electrophysiology
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins / physiology*
  • Gene Transfer Techniques
  • Ion Channel Gating*
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Peptide Fragments / metabolism
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Muscarinic / physiology
  • Recombinant Fusion Proteins / metabolism
  • Spodoptera / metabolism
  • Xenopus laevis


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Peptide Fragments
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Muscarinic
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins