Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies

Neuron. 2002 Jun 13;34(6):933-44. doi: 10.1016/s0896-6273(02)00725-0.


Inwardly rectifying K(+) (Kir) channels are important regulators of resting membrane potential and cell excitability. The activity of Kir channels is critically dependent on the integrity of channel interactions with phosphatidylinositol 4,5-bisphosphate (PIP(2)). Here we identify and characterize channel-PIP(2) interactions that are conserved among Kir family members. We find basic residues that interact with PIP(2), two of which have been associated with Andersen's and Bartter's syndromes. We show that several naturally occurring mutants decrease channel-PIP(2) interactions, leading to disease.

Publication types

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

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Bartter Syndrome / genetics
  • Bartter Syndrome / metabolism
  • Conserved Sequence / genetics*
  • Female
  • Glycogen Storage Disease Type IV / genetics
  • Glycogen Storage Disease Type IV / metabolism
  • Ion Channel Gating / genetics
  • Membrane Potentials / genetics
  • Molecular Sequence Data
  • Mutation / genetics
  • Oocytes / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Xenopus laevis


  • Phosphatidylinositol 4,5-Diphosphate
  • Potassium Channels, Inwardly Rectifying