Imperial College London

ProfessorDavidCarling

Faculty of MedicineInstitute of Clinical Sciences

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 3313 4313david.carling

 
 
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Location

 

3rd Fl CRBHammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Yavari:2017:10.1038/s41467-017-01342-5,
author = {Yavari, A and Bellahcene, M and Bucchi, A and Sirenko, S and Pinter, K and Herring, N and Jung, JJ and Tarasov, KV and Sharpe, EJ and Wolfien, M and Czibik, G and Steeples, V and Ghaffari, S and Nguyen, C and Stockenhuber, A and Clair, JRS and Rimmbach, C and Okamoto, Y and Yang, D and Wang, M and Ziman, BD and Moen, JM and Riordon, DR and Ramirez, C and Paina, M and Lee, J and Zhang, J and Ahmet, I and Matt, MG and Tarasova, YS and Baban, D and Sahgal, N and Lockstone, H and Puliyadi, R and de, Bono J and Siggs, OM and Gomes, J and Muskett, H and Maguire, ML and Beglov, Y and Kelly, M and Dos, Santos PPN and Bright, NJ and Woods, A and Gehmlich, K and Isackson, H and Douglas, G and Ferguson, DJP and Schneider, JE and Tinker, A and Wolkenhauer, O and Channon, KM and Cornall, RJ and Sternick, EB and Paterson, DJ and Redwood, CS and Carling, D and Proenza, C and David, R and Baruscotti, M and DiFrancesco, D and Lakatta, EG and Watkins, H and Ashrafian, H},
doi = {10.1038/s41467-017-01342-5},
journal = {Nature Communications},
title = {Mammalian γ2 AMPK regulates intrinsic heart rate.},
url = {http://dx.doi.org/10.1038/s41467-017-01342-5},
volume = {8},
year = {2017}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - 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 Ca(2+) 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.
AU - Yavari,A
AU - Bellahcene,M
AU - Bucchi,A
AU - Sirenko,S
AU - Pinter,K
AU - Herring,N
AU - Jung,JJ
AU - Tarasov,KV
AU - Sharpe,EJ
AU - Wolfien,M
AU - Czibik,G
AU - Steeples,V
AU - Ghaffari,S
AU - Nguyen,C
AU - Stockenhuber,A
AU - Clair,JRS
AU - Rimmbach,C
AU - Okamoto,Y
AU - Yang,D
AU - Wang,M
AU - Ziman,BD
AU - Moen,JM
AU - Riordon,DR
AU - Ramirez,C
AU - Paina,M
AU - Lee,J
AU - Zhang,J
AU - Ahmet,I
AU - Matt,MG
AU - Tarasova,YS
AU - Baban,D
AU - Sahgal,N
AU - Lockstone,H
AU - Puliyadi,R
AU - de,Bono J
AU - Siggs,OM
AU - Gomes,J
AU - Muskett,H
AU - Maguire,ML
AU - Beglov,Y
AU - Kelly,M
AU - Dos,Santos PPN
AU - Bright,NJ
AU - Woods,A
AU - Gehmlich,K
AU - Isackson,H
AU - Douglas,G
AU - Ferguson,DJP
AU - Schneider,JE
AU - Tinker,A
AU - Wolkenhauer,O
AU - Channon,KM
AU - Cornall,RJ
AU - Sternick,EB
AU - Paterson,DJ
AU - Redwood,CS
AU - Carling,D
AU - Proenza,C
AU - David,R
AU - Baruscotti,M
AU - DiFrancesco,D
AU - Lakatta,EG
AU - Watkins,H
AU - Ashrafian,H
DO - 10.1038/s41467-017-01342-5
PY - 2017///
SN - 2041-1723
TI - Mammalian γ2 AMPK regulates intrinsic heart rate.
T2 - Nature Communications
UR - http://dx.doi.org/10.1038/s41467-017-01342-5
UR - http://hdl.handle.net/10044/1/53306
VL - 8
ER -