Identification of structural elements involved in G protein gating of the GIRK1 potassium channel

Neuron. 1995 Nov;15(5):1145-56. doi: 10.1016/0896-6273(95)90102-7.


Chimeras of GIRK1 and IRK1, a G protein-insensitive inward rectifier, are activated by coexpression of G beta gamma if they contain either the N-terminal or part of the C-terminal hydrophilic domain of GIRK1. The N-terminal domain of GIRK1 also facilitates the fast rates of activation and deactivation following m2 muscarinic receptor stimulation. The hydrophobic core of GIRK1 (M1-H5-M2) is important for determining the brief single-channel open times typical of GIRK1 but not important for determining G beta gamma sensitivity. Coexpression with CIR revealed that the gating properties associated with different GIRK1 domains could not have arisen from altered ability to form heteromultimers. These results implicate specific regions of GIRK1 in G protein activation and suggest that GIRK1 may be closely linked to the m2 muscarinic receptor-G protein complex.

Publication types

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

MeSH terms

  • Animals
  • Carbachol / pharmacology
  • Electric Conductivity
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins / physiology*
  • Gene Expression
  • Gene Transfer Techniques
  • Ion Channel Gating / physiology*
  • Macromolecular Substances
  • Mutagenesis
  • Oocytes / physiology
  • Peptide Fragments / physiology
  • Polymerase Chain Reaction
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Muscarinic / physiology
  • Recombinant Fusion Proteins
  • Structure-Activity Relationship
  • Xenopus laevis


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