Gating of inwardly rectifying K+ channels localized to a single negatively charged residue

Nature. 1994 Sep 15;371(6494):246-9. doi: 10.1038/371246a0.


Inwardly rectifying K+ channels (IRKs) conduct current preferentially in the inward direction. This inward rectification has two components: voltage-dependent blockade by intracellular Mg2+ (Mg2+i) and intrinsic gating. Two members of this channel family, IRK1 (ref. 10) and ROMK1 (ref. 11), differ markedly in affinity for Mg2+i (ref. 12). We found that IRK1 and ROMK1 differ in voltage-dependent gating and searched for the gating structure by large-scale and site-directed mutagenesis. We found that a single amino-acid change within the putative transmembrane domain M2, aspartate (D) in IRK1 to the corresponding asparagine (N) in ROMK1, controls the gating phenotype. Mutation D172N in IRK1 produced ROMK1-like gating whereas the reverse mutation in ROMK1--N171D--produced IRK1-like gating. Thus, a single negatively charged residue seems to be a crucial determinant of gating.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cells, Cultured
  • Humans
  • Ion Channel Gating*
  • Magnesium / metabolism
  • Membrane Potentials
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Xenopus


  • KCNJ1 protein, human
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Recombinant Fusion Proteins
  • Magnesium