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Life Sci. 2014 Mar 11;98(2):75-82. doi: 10.1016/j.lfs.2014.01.006. Epub 2014 Jan 19.

Alpha1 catalytic subunit of AMPK modulates contractile function of cardiomyocytes through phosphorylation of troponin I.

Author information

1
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo - State University of New York, Buffalo, NY, United States.
2
Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
3
Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin - Madison, WI, United States.
4
Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: zhuangjianzggd@yahoo.cn.
5
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo - State University of New York, Buffalo, NY, United States. Electronic address: jli23@buffalo.edu.

Abstract

AIMS:

The specific role of AMPKα1 or AMPKα2 in mediating cardiomyocyte contractile function remains elusive. The present study investigated how AMPK activation modulates the contractility of isolated cardiomyocytes.

MAIN METHODS:

Mechanical properties and intracellular Ca(2+) properties were measured in isolated cardiomyocytes. The stress signaling was evaluated using western blot and immunoprecipitation analysis.

KEY FINDINGS:

AMPK activator, A-769662 induced maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt), peak height and peak shortening (PS) amplitude in both WT and AMPKα2 KO cardiomyocytes, but did not affect time-to-90% relengthening (TR90). AMPK KD cardiomyocytes demonstrated contractile dysfunction compared with cardiomyocytes from WT and AMPKα2 KO hearts. However, the rise of intracellular Ca(2+) levels as well as intracellular ATP levels has no significant difference among WT, AMPKα2 KO and AMPK KD groups with and without the presence of A-769662. Besides, WT, AMPKα2 KO and AMPK KD group displayed a phosphorylated AMPK and downstream acetyl-CoA carboxylase (ACC) phosphorylation. Interestingly, A-769662 also triggered troponin I (cTnI) phosphorylation at Ser(149) site which is related to contractility of cardiomyocytes. Furthermore, the immunoprecipitation analysis revealed that AMPKα1 of cardiomyocytes was phosphorylated by A-769662.

SIGNIFICANCE:

This is the first study illustrating that activation of AMPK plays a significant role in mediating the contractile function of cardiomyocytes using transgenic animal models. AMPK activator facilitates the contractility of cardiomyocytes via activating AMPKα1 catalytic subunit. The phosphorylation of cTnI by AMPK could be a factor attributing to the regulation of contractility of cardiomyocytes.

KEYWORDS:

AMPK; Contractile function; Troponin I

PMID:
24447627
PMCID:
PMC4777330
DOI:
10.1016/j.lfs.2014.01.006
[Indexed for MEDLINE]
Free PMC Article

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