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

• Published in: Life sciences (1973) Vol. 98; no. 2; pp. 75 - 82
• Main Authors: Chen, Si, Zhu, Ping, Guo, Hui-Ming, Solis, Raquel Sancho, Wang, Yanqing, Ma, Yina, Wang, Jinli, Gao, Junjie, Chen, Ji-Mei, Ge, Ying, Zhuang, Jian, Li, Ji
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 11.03.2014
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Biphenyl Compounds; Contractile function; Immunoblotting; Male; Mice; Mice, Knockout; Mice, Transgenic; Myocardial Contraction - drug effects; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - enzymology; Phosphorylation; Pyrones - pharmacology; Signal Transduction - drug effects; Thiophenes - pharmacology; Troponin I; Troponin I - metabolism; Troponin I; AMPK; Contractile function
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2014.01.006

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. Mechanical properties and intracellular Ca2+ properties were measured in isolated cardiomyocytes. The stress signaling was evaluated using western blot and immunoprecipitation analysis. 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 Ca2+ 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 Ser149 site which is related to contractility of cardiomyocytes. Furthermore, the immunoprecipitation analysis revealed that AMPKα1 of cardiomyocytes was phosphorylated by A-769662. 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.