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

Hidetada Yoshida, Li Bao, Eirini Kefaloyianni, Eylem Taskin, Uzoma Okorie, Miyoun Hong, Piyali Dhar-Chowdhury, Michiyo Kaneko, William A. Coetzee

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

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".

Original languageEnglish
Pages (from-to)410-418
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • AMP-activated protein kinase
  • ATP-sensitive K channels
  • Energy metabolism
  • Local signaling
  • Potassium channels

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    Yoshida, H., Bao, L., Kefaloyianni, E., Taskin, E., Okorie, U., Hong, M., Dhar-Chowdhury, P., Kaneko, M., & Coetzee, W. A. (2012). AMP-activated protein kinase connects cellular energy metabolism to K ATP channel function. Journal of Molecular and Cellular Cardiology, 52(2), 410-418. https://doi.org/10.1016/j.yjmcc.2011.08.013