Imperial College London
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Emeritus ProfessorKenMacLeod

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor of Cardiac Physiology
 
 
 
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Contact

 

+44 (0)20 7594 2734k.t.macleod

 
 
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Assistant

 

Miss Natasha Richmond +44 (0)20 7594 6457

 
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Location

 

336ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ke:2020:10.1113/jp277038,
author = {Ke, H-Y and Yang, H-S and Francis, AJ and Collins, TP and Surendran, H and Alvarez-Laviada, A and Firth, JM and MacLeod, KT},
doi = {10.1113/jp277038},
journal = {The Journal of Physiology},
pages = {1339--1359},
title = {Changes in cellular Ca2+ and Na+ regulation during the progression towards heart failure in the guinea pig},
url = {http://dx.doi.org/10.1113/jp277038},
volume = {598},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - We followed changes in cardiac myocyte Ca2+ and Na+ regulation from the formation of compensated hypertrophy (CH) until signs of heart failure (HF) are apparent using a transaortic pressure overload (TAC) model. In this model, in vivo fractional shortening (FS) remained constant despite HW:BW ratio increasing by 39% (CH) until HF developed 150 days postTAC when FS decreased from 70% to 39%. Using live and fixed fluorescence imaging and electrophysiological techniques, we found an increase in INa,late from –0.34 to –0.59 A F−1 and a decrease in Na+,K+ATPase current from 1.09 A F−1 to 0.54 A F−1 during CH. These changes persisted as HF developed (INa,late increased to –0.82 A F−1 and Na+,K+ATPase current decreased to 0.51 A F−1). Sarcoplasmic reticulum (SR) Ca2+ content increased during CH then decreased in HF (from 32 to 15 μm l−1) potentially supporting the maintenance of FS in the whole heart and Ca2+ transients in single myocytes during the former stage. We showed using glycoside blockade in healthy myocytes that increases in SR Ca2+ content and Ca2+ transients can be driven by the same amount of inhibition of the Na+,K+ATPase as measured in the diseased cells. SERCA function remains constant in CH but decreases (τ for SERCAmediated Ca2+ removal changed from 6.3 to 3.0 s−1) in HF. In HF there was an increase in spark frequency and sparkmediated Ca2+ leak. We suggest an increase in INa,late and a decrease in Na+,K+ATPase current and function alters the balance of Ca2+ flux mediated by the Na+/Ca2+ exchange that limits early contractile impairment.
AU  - Ke,H-Y
AU  - Yang,H-S
AU  - Francis,AJ
AU  - Collins,TP
AU  - Surendran,H
AU  - Alvarez-Laviada,A
AU  - Firth,JM
AU  - MacLeod,KT
DO  - 10.1113/jp277038
EP  - 1359
PY  - 2020///
SN  - 0022-3751
SP  - 1339
TI  - Changes in cellular Ca2+ and Na+ regulation during the progression towards heart failure in the guinea pig
T2  - The Journal of Physiology
UR  - http://dx.doi.org/10.1113/jp277038
UR  - http://hdl.handle.net/10044/1/68404
VL  - 598
ER  -
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