Adenosine-triphosphate-sensitive K+ channel (Kir6.1): a novel phosphospecific interaction partner of connexin 43 (Cx43)

Exp Cell Res. 2012 Dec 10;318(20):2559-66. doi: 10.1016/j.yexcr.2012.08.004. Epub 2012 Aug 30.


Connexin 43 (Cx43) is a phosphoprotein expressed in a wide variety of cells. Cx43 and adenosine-triphosphate-sensitive K(+)channels [K(+)(ATP)] are part of same signaling pathway that regulates cell survival during stress and ischemia preconditioning. Molecular mechanism for their coordinated role in ischemia/hypoxia preconditioning is not well known. Using pull down, co-immunoprecipitation assays and co-localization studies we provide evidence, for the first time that Kir6.1, a K(+)(ATP) channel protein component, can interact with Cx43. Further we show that the interaction was phospho-specific such that Cx43 phosphorylated at serine 262 (S262) interacted with Kir6.1 in preference to the unphosphorylated form of Cx43. Introduction of phospho-deficient mutation at serine 262 (S262A) in Cx43 completely abolished the interaction. Our data provide an interesting lead about a possible partnership between Cx43 and Kir6.1, which will help in better understanding their role in ischemia/hypoxia preconditioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / toxicity*
  • Animals
  • Connexin 43 / genetics
  • Connexin 43 / metabolism*
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Ischemia / genetics
  • Ischemia / metabolism*
  • Ischemic Preconditioning / methods*
  • KATP Channels / genetics
  • KATP Channels / metabolism*
  • Mice
  • Mutagenesis, Site-Directed
  • NIH 3T3 Cells
  • Phosphorylation / genetics


  • Connexin 43
  • GJA1 protein, mouse
  • KATP Channels
  • uK-ATP-1 potassium channel
  • Adenosine Triphosphate