AMP-activated protein kinase connects cellular energy metabolism to KATP channel function

J Mol Cell Cardiol. 2012 Feb;52(2):410-8. doi: 10.1016/j.yjmcc.2011.08.013. Epub 2011 Aug 24.


AMPK is an important sensor of cellular energy levels. The aim of these studies was to investigate whether cardiac K(ATP) channels, which couple cellular energy metabolism to membrane excitability, are regulated by AMPK activity. We investigated effects of AMPK on rat ventricular K(ATP) channels using electrophysiological and biochemical approaches. Whole-cell K(ATP) channel current was activated by metabolic inhibition; this occurred more rapidly in the presence of AICAR (an AMPK activator). AICAR had no effects on K(ATP) channel activity recorded in the inside-out patch clamp configuration, but ZMP (the intracellular intermediate of AICAR) strongly activated K(ATP) channels. An AMPK-mediated effect is demonstrated by the finding that ZMP had no effect on K(ATP) channels in the presence of Compound C (an AMPK inhibitor). Recombinant AMPK activated Kir6.2/SUR2A channels in a manner that was dependent on the AMP concentration, whereas heat-inactivated AMPK was without effect. Using mass-spectrometry and co-immunoprecipitation approaches, we demonstrate that the AMPK α-subunit physically associates with K(ATP) channel subunits. Our data demonstrate that the cardiac K(ATP) channel function is directly regulated by AMPK activation. During metabolic stress, a small change in cellular AMP that activates AMPK can be a potential trigger for K(ATP) channel opening. This article is part of a Special Issue entitled "Local Signaling in Myocytes".

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Adenosine Monophosphate / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Energy Metabolism / physiology*
  • KATP Channels / agonists
  • KATP Channels / genetics
  • KATP Channels / metabolism*
  • Male
  • Mice
  • Myocytes, Cardiac / metabolism
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleotides / pharmacology
  • Signal Transduction
  • Stress, Physiological


  • KATP Channels
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Adenosine Monophosphate
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide