Control of rectification and permeation by residues in two distinct domains in an inward rectifier K+ channel

Neuron. 1995 May;14(5):1047-54. doi: 10.1016/0896-6273(95)90343-7.


Inwardly rectifying K+ channels conduct more inward than outward current as a result of voltage-dependent block of the channel pore by intracellular Mg2+ and polyamines. We investigated the molecular mechanism and structural determinants of inward rectification and ion permeation in a strongly rectifying channel, IRK1. Block by Mg2+ and polyamines is found not to conform to one-to-one binding, suggesting that a channel pore can accommodate more than one blocking particle. A negatively charged amino acid in the hydrophilic C-terminal domain is found to be critical for both inward rectification and ion permeation. This residue and a negatively charged residue in the putative second transmembrane segment (M2) contribute independently to high affinity binding of Mg2+ and polyamines. Mutation of this residue also induces Mg(2+)- and polyamine-independent inward rectification and dramatically alters single-channel behavior. We propose that the hydrophilic C-terminal domain comprises part of the channel pore and that involvement of both hydrophilic and hydrophobic domains in pore lining may provide a molecular basis for the multi-ion, long-pore nature of inwardly rectifying K+ channels.

Publication types

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

MeSH terms

  • Amino Acids / chemistry
  • Animals
  • Electric Conductivity
  • Electrochemistry
  • Female
  • Magnesium / metabolism
  • Magnesium / pharmacology
  • Mutagenesis, Insertional
  • Mutagenesis, Site-Directed
  • Oocytes / metabolism
  • Polyamines / metabolism
  • Polyamines / pharmacology
  • Polymerase Chain Reaction
  • Potassium / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / genetics
  • Potassium Channels / physiology*
  • Spermidine / metabolism
  • Spermidine / pharmacology
  • Structure-Activity Relationship
  • Thermodynamics
  • Xenopus laevis


  • Amino Acids
  • Polyamines
  • Potassium Channels
  • Magnesium
  • Potassium
  • Spermidine