TY - JOUR
T1 - AMP-activated protein kinase connects cellular energy metabolism to K ATP channel function
AU - Yoshida, Hidetada
AU - Bao, Li
AU - Kefaloyianni, Eirini
AU - Taskin, Eylem
AU - Okorie, Uzoma
AU - Hong, Miyoun
AU - Dhar-Chowdhury, Piyali
AU - Kaneko, Michiyo
AU - Coetzee, William A.
N1 - Funding Information:
These studies were supported by the National Institutes of Health ( HL064838 and HL085820 ), the American Heart Association (Established Investigator Award to WAC) and in part by the New York Masonic Seventh District Association, Inc .
PY - 2012/2
Y1 - 2012/2
N2 - 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".
AB - 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".
KW - AMP-activated protein kinase
KW - ATP-sensitive K channels
KW - Energy metabolism
KW - Local signaling
KW - Potassium channels
UR - http://www.scopus.com/inward/record.url?scp=84855987574&partnerID=8YFLogxK
U2 - 10.1016/j.yjmcc.2011.08.013
DO - 10.1016/j.yjmcc.2011.08.013
M3 - Article
C2 - 21888913
AN - SCOPUS:84855987574
SN - 0022-2828
VL - 52
SP - 410
EP - 418
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 2
ER -