Skip Navigation


Cardiovascular Research Advance Access originally published online on August 21, 2007
Cardiovascular Research 2008 77(2):302-314; doi:10.1093/cvr/cvm006
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
77/2/302    most recent
cvm006v2
cvm006v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by George, C. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by George, C. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For Permissions please e-mail: journals.permissions@oxfordjournals.org

Sarcoplasmic reticulum Ca2+ leak in heart failure: mere observation or functional relevance?

Christopher H. George*

Wales Heart Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK

* Corresponding author. Tel: +44 2920 744431; fax: +44 2920 743500. E-mail address: georgech{at}cf.ac.uk

Heart failure (HF) is a chronic multi-factorial disease characterized by sarcoplasmic reticulum (SR) dysfunction that manifests as severely reduced contractility and increased risk of arrhythmia. Several lines of evidence have revealed the existence of defective ryanodine receptor (RyR2)-mediated Ca2+ leak in HF, although its relevance as a causative factor rather than a phenotypic consequence of the disease is questioned. This review will consider the relative contribution of RyR2-mediated Ca2+ leak to the profound cellular, transcriptional and electrical remodelling associated with HF. In particular, it will focus on our current understanding of the role of defective phosphorylation of RyR2 as a both a chronic mediator of excitation–contraction coupling (ECC) dysfunction and as a potent catalyst of RyR2-dependent arrhythmogenesis. A hypothetical concept that SR Ca2+ leak fundamentally underlies the increased arrhythmogenic susceptibility in HF, but that it may not directly contribute to contractile dysfunction, which may involve maladaptive perturbations in metabolism and energy utilization, is also discussed.

KEYWORDS Sarcoplasmic reticulum; Ryanodine receptor; Calcium handling; Arrhythmia

Time for primary review: 26 days


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Physiol.Home page
T. L. Domeier, L. A. Blatter, and A. V. Zima
Alteration of sarcoplasmic reticulum Ca2+ release termination by ryanodine receptor sensitization and in heart failure
J. Physiol., November 1, 2009; 587(21): 5197 - 5209.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
T. J. Pritchard and E. G. Kranias
Junctin and the histidine-rich Ca2+ binding protein: potential roles in heart failure and arrhythmogenesis
J. Physiol., July 1, 2009; 587(13): 3125 - 3133.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. Lee, M. A. Stagg, S. Fukushima, G. K. R. Soppa, U. Siedlecka, S. J. Youssef, K. Suzuki, M. H. Yacoub, and C. M. N. Terracciano
Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes
Am J Physiol Heart Circ Physiol, April 1, 2009; 296(4): H927 - H936.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. V. Zima, J. Qin, M. Fill, and L. A. Blatter
Tricyclic antidepressant amitriptyline alters sarcoplasmic reticulum calcium handling in ventricular myocytes
Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2008 - H2016.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. V. Zima, E. Picht, D. M. Bers, and L. A. Blatter
Termination of Cardiac Ca2+ Sparks: Role of Intra-SR [Ca2+], Release Flux, and Intra-SR Ca2+ Diffusion
Circ. Res., October 10, 2008; 103(8): e105 - e115.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. Garcia-Dorado, H. M. Piper, and D. A. Eisner
Sarcoplasmic reticulum and mitochondria in cardiac pathophysiology
Cardiovasc Res, January 15, 2008; 77(2): 231 - 233.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.