Mammalian γ2 AMPK regulates intrinsic heart rate

Arash Yavari (), Mohamed Bellahcene, Annalisa Bucchi, Syevda Sirenko, Katalin Pinter, Neil Herring, Julia J. Jung, Kirill V. Tarasov, Emily J. Sharpe, Markus Wolfien, Gabor Czibik, Violetta Steeples, Sahar Ghaffari, Chinh Nguyen, Alexander Stockenhuber, Joshua R. St. Clair, Christian Rimmbach, Yosuke Okamoto, Dongmei Yang, Mingyi Wang, Bruce D. Ziman, Jack M. Moen, Daniel R. Riordon, Christopher Ramirez, Manuel Paina, Joonho Lee, Jing Zhang, Ismayil Ahmet, Michael G. Matt, Yelena S. Tarasova, Dilair Baban, Natasha Sahgal, Helen Lockstone, Rathi Puliyadi, Joseph Bono, Owen M. Siggs, John Gomes, Hannah Muskett, Mahon L. Maguire, Youlia Beglov, Matthew Kelly, Pedro P. N. Santos, Nicola J. Bright, Angela Woods, Katja Gehmlich, Henrik Isackson, Gillian Douglas, David J. P. Ferguson, Jürgen E. Schneider, Andrew Tinker, Olaf Wolkenhauer, Keith M. Channon, Richard J. Cornall, Eduardo B. Sternick, David J. Paterson, Charles S. Redwood, David Carling, Catherine Proenza, Robert David, Mirko Baruscotti, Dario DiFrancesco, Edward G. Lakatta, Hugh Watkins and Houman Ashrafian ()
Additional contact information
Arash Yavari: Experimental Therapeutics, Radcliffe Department of Medicine, University of Oxford
Mohamed Bellahcene: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Annalisa Bucchi: Università degli Studi di Milano
Syevda Sirenko: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Katalin Pinter: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Neil Herring: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy & Genetics, University of Oxford
Julia J. Jung: Rostock University Medical Centre
Kirill V. Tarasov: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Emily J. Sharpe: University of Colorado School of Medicine
Markus Wolfien: University of Rostock
Gabor Czibik: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Violetta Steeples: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Sahar Ghaffari: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Chinh Nguyen: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Alexander Stockenhuber: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Joshua R. St. Clair: University of Colorado School of Medicine
Christian Rimmbach: Rostock University Medical Centre
Yosuke Okamoto: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Dongmei Yang: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Mingyi Wang: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Bruce D. Ziman: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Jack M. Moen: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Daniel R. Riordon: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Christopher Ramirez: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Manuel Paina: Università degli Studi di Milano
Joonho Lee: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Jing Zhang: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Ismayil Ahmet: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Michael G. Matt: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Yelena S. Tarasova: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Dilair Baban: The Wellcome Trust Centre for Human Genetics
Natasha Sahgal: The Wellcome Trust Centre for Human Genetics
Helen Lockstone: The Wellcome Trust Centre for Human Genetics
Rathi Puliyadi: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Joseph Bono: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Owen M. Siggs: The Wellcome Trust Centre for Human Genetics
John Gomes: BHF Laboratories, The Rayne Institute, University College London
Hannah Muskett: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Mahon L. Maguire: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Youlia Beglov: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Matthew Kelly: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Pedro P. N. Santos: Instituto de Pós-Graduação, Faculdade de Ciências Médicas de Minas Gerais
Nicola J. Bright: Cellular Stress Group, MRC London Institute of Medical Sciences, Imperial College London
Angela Woods: Cellular Stress Group, MRC London Institute of Medical Sciences, Imperial College London
Katja Gehmlich: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Henrik Isackson: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Gillian Douglas: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
David J. P. Ferguson: Nuffield Department of Clinical Laboratory Science, University of Oxford
Jürgen E. Schneider: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Andrew Tinker: BHF Laboratories, The Rayne Institute, University College London
Olaf Wolkenhauer: University of Rostock
Keith M. Channon: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Richard J. Cornall: The Wellcome Trust Centre for Human Genetics
Eduardo B. Sternick: Instituto de Pós-Graduação, Faculdade de Ciências Médicas de Minas Gerais
David J. Paterson: Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy & Genetics, University of Oxford
Charles S. Redwood: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
David Carling: Cellular Stress Group, MRC London Institute of Medical Sciences, Imperial College London
Catherine Proenza: University of Colorado School of Medicine
Robert David: Rostock University Medical Centre
Mirko Baruscotti: Università degli Studi di Milano
Dario DiFrancesco: Università degli Studi di Milano
Edward G. Lakatta: Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH
Hugh Watkins: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford
Houman Ashrafian: Experimental Therapeutics, Radcliffe Department of Medicine, University of Oxford

Nature Communications, 2017, vol. 8, issue 1, 1-19

Abstract: Abstract AMPK is a conserved serine/threonine kinase whose activity maintains cellular energy homeostasis. Eukaryotic AMPK exists as αβγ complexes, whose regulatory γ subunit confers energy sensor function by binding adenine nucleotides. Humans bearing activating mutations in the γ2 subunit exhibit a phenotype including unexplained slowing of heart rate (bradycardia). Here, we show that γ2 AMPK activation downregulates fundamental sinoatrial cell pacemaker mechanisms to lower heart rate, including sarcolemmal hyperpolarization-activated current (I f) and ryanodine receptor-derived diastolic local subsarcolemmal Ca2+ release. In contrast, loss of γ2 AMPK induces a reciprocal phenotype of increased heart rate, and prevents the adaptive intrinsic bradycardia of endurance training. Our results reveal that in mammals, for which heart rate is a key determinant of cardiac energy demand, AMPK functions in an organ-specific manner to maintain cardiac energy homeostasis and determines cardiac physiological adaptation to exercise by modulating intrinsic sinoatrial cell behavior.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-01342-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01342-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-01342-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().