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Exercise-induced increases in the expression and activity of cardiac sarcoplasmic reticulum calcium ATPase 2 is attenuated in AMPKα2 kinase-dead mice.

  • Morissette, Marc P1, 2
  • Susser, Shanel E1, 2, 3
  • Stammers, Andrew N1, 2
  • Moffatt, Teri L1, 2
  • Wigle, Jeffrey T1, 4
  • Wigle, Theodore J1, 2, 3
  • Netticadan, Thomas3, 5, 6
  • Premecz, Sheena1
  • Jassal, Davinder S1, 5, 7
  • O'Hara, Kimberley A1, 2
  • Duhamel, Todd A1, 2, 3
  • 1 a Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, 351 Tache Avenue, Winnipeg, MB R2H 2A6, Canada. , (Canada)
  • 2 b Health, Leisure, and Human Performance Research Institute, Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB R3T 2N2, Canada. , (Canada)
  • 3 c Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. , (Canada)
  • 4 d Department of Biochemistry and Medical Genetics, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R2E 3N4, Canada. , (Canada)
  • 5 e Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Albrechtsen Research Centre, Winnipeg, MB R2H 2A6, Canada. , (Canada)
  • 6 f Agriculture and Agri-Food Canada, Winnipeg, MB R3C 3G7, Canada. , (Canada)
  • 7 g Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3A 1R9, Canada. , (Canada)
Published Article
Canadian Journal of Physiology and Pharmacology
Canadian Science Publishing
Publication Date
Aug 01, 2019
DOI: 10.1139/cjpp-2018-0737
PMID: 31237455


Exercise enhances cardiac sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) function through unknown mechanisms. The present study tested the hypothesis that the positive effects of exercise on SERCA2a expression and function in the left ventricle is dependent on adenosine-monophosphate-activated protein kinase (AMPK) α2 function. AMPKα2 kinase-dead (KD) transgenic mice, which overexpress inactivated AMPKα2 subunit, and wild-type C57Bl/6 (WT) mice were randomized into sedentary groups or groups with access to running wheels. After 5 months, exercised KD mice exhibited shortened deceleration time compared with sedentary KD mice. In left ventricular tissue, the ratio of phosphorylated AMPKαThr172:total AMPKα was 65% lower (P < 0.05) in KD mice compared with WT mice. The left ventricle of KD mice had 37% lower levels of SERCA2a compared with WT mice. Although exercise increased SERCA2a protein levels in WT mice by 53%, this response of exercise was abolished in exercised KD mice. Exercise training reduced total phospholamban protein content by 23% in both the WT and KD mice but remained 20% higher overall in KD mice. Collectively, these data suggest that AMPKα influences SERCA2a and phospholamban protein content in the sedentary and exercised heart, and that exercise-induced changes in SERCA2a protein are dependent on AMPKα function.

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