Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution

Cell. 2002 Dec 27;111(7):957-65. doi: 10.1016/s0092-8674(02)01227-8.


Inward rectifier K(+) channels govern the resting membrane voltage in many cells. Regulation of these ion channels via G protein-coupled receptor signaling underlies the control of heart rate and the actions of neurotransmitters in the central nervous system. We have determined the protein structure formed by the intracellular N- and C termini of the G protein-gated inward rectifier K(+) channel GIRK1 at 1.8 A resolution. A cytoplasmic pore, conserved among inward rectifier K(+) channels, extends the ion pathway to 60 A, nearly twice the length of a canonical transmembrane K(+) channel. The cytoplasmic pore is lined by acidic and hydrophobic amino acids, creating a favorable environment for polyamines, which block the pore. These results explain in structural and chemical terms the basis of inward rectification, and they also have implications for G protein regulation of GIRK channels.

Publication types

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

MeSH terms

  • Amino Acid Sequence / physiology
  • Amino Acids / chemistry
  • Animals
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Cytoplasm / metabolism*
  • Cytoplasm / ultrastructure
  • Eukaryotic Cells / metabolism*
  • Eukaryotic Cells / ultrastructure
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins / metabolism*
  • Membrane Potentials / physiology
  • Mice
  • Polyamines / pharmacology
  • Potassium Channels / metabolism*
  • Potassium Channels / ultrastructure
  • Potassium Channels, Inwardly Rectifying*
  • Protein Structure, Tertiary / physiology


  • Amino Acids
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Kcnj3 protein, mouse
  • Polyamines
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • GTP-Binding Proteins

Associated data

  • PDB/1N9P