title: AMP-activated protein kinase connects cellular energy metabolism to KATP channel function.
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".
authors: Pediatric Cardiology, NYU School of Medicine, New York, NY 10016, USA.
authors: Hidetada
authors: H
authors: Yoshida
authors: Li
authors: L
authors: Bao
authors: Eirini
authors: E
authors: Kefaloyianni
authors: Eylem
authors: E
authors: Taskin
authors: Uzoma
authors: U
authors: Okorie
authors: Miyoun
authors: M
authors: Hong
authors: Piyali
authors: P
authors: Dhar-Chowdhury
authors: Michiyo
authors: M
authors: Kaneko
authors: William A
authors: WA
authors: Coetzee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004734:Energy Metabolism / Q000502:physiology*; D054086:KATP Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D054086:KATP Channels; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide