Identification of domains conferring G protein regulation on inward rectifier potassium channels

Cell. 1995 Nov 3;83(3):443-9. doi: 10.1016/0092-8674(95)90122-1.


Cardiac m2 muscarinic acetylcholine receptors reduce heart rate by coupling to heterotrimeric (alpha beta gamma) guanine nucleotide-binding (G) proteins that activate IKACh, an inward rectifier K+ channel (IRK). Activation of the GIRK subunit of IKACh requires G beta gamma subunits; however, the structural basis of channel regulation is unknown. To determine which sequences confer G beta gamma regulation upon IRKs, we generated chimeric proteins composed of GIRK and RB-IRK2, a related, G protein-insensitive channel. Importantly, a chimeric channel containing the hydrophobic pore region of RB-IRK2 joined to the amino and carboxyl termini of GIRK exhibited voltage- and receptor-dependent activation in Xenopus oocytes. Furthermore, carboxy-terminal sequences specific to this chimera and GIRK bound G beta gamma subunits in vitro. Thus, G beta gamma may regulate IRKs by interacting with sequences adjacent to the putative channel pore.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytoplasm / metabolism
  • Electrophysiology
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / physiology*
  • Molecular Sequence Data
  • Oocytes / physiology
  • Potassium Channels / chemistry
  • Potassium Channels / physiology*
  • Potassium Channels / ultrastructure
  • Protein Binding / physiology
  • Recombinant Fusion Proteins / physiology
  • Xenopus laevis


  • Potassium Channels
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins

Associated data

  • GENBANK/L25264
  • GENBANK/L35771
  • GENBANK/X78461