Skip Navigation


Cardiovascular Research Advance Access originally published online on April 23, 2009
Cardiovascular Research 2009 83(1):89-96; doi:10.1093/cvr/cvp125
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
83/1/89    most recent
cvp125v2
cvp125v1
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 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 arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Kuum, M.
Right arrow Articles by Veksler, V.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kuum, M.
Right arrow Articles by Veksler, V.
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 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources

Malle Kuum1,2,3, Allen Kaasik1,2,3, Frederic Joubert1,2, Renée Ventura-Clapier1,2 and Vladimir Veksler1,2,*

1 Faculté de Pharmacie, U-769 INSERM, Université Paris-Sud, Châtenay-Malabry F-92296, France
2 Univ Paris-Sud, Châtenay-Malabry F-92296, France
3 Department of Pharmacology, Centre of Molecular and Clinical Medicine, University of Tartu, Tartu, Estonia

* Corresponding author. Tel: +33 1 4683 5763; fax: +33 1 4683 5475.E-mail address: vladimir.veksler{at}cep.u-psud.fr

Aims: Increased diastolic sarcoplasmic reticulum (SR) Ca2+ loss could depress contractility in heart failure. Since the failing myocardium has impaired energetics, we investigated whether Ca2+ loss is linked to changes in energetic pathways.

Methods and results: Leakage from SR in mouse permeabilized preparations was assessed using exogenous ATP, ATP + phosphocreatine (activation of bound creatine kinase, CK), ATP + mitochondrial substrates (mitochondrial activation), or with all of these together (optimal energetic conditions) in Ca2+-free solution. In ventricular fibres caffeine-induced tension transients under optimal energetic conditions were used to estimate SR [Ca2+]. In cardiomyocytes, intra-SR Ca2+ was monitored by use of the fluorescent marker Mag-fluo 4. In fibres, SR Ca2+ content after 5 min incubation strongly depended on energy supply (100%—optimal energetic conditions; 27 ± 5%—exogenous ATP only, 52 ± 5%—endogenous CK activation; 88 ± 8%—mitochondrial activation, P < 0.01 vs. CK system). The significant loss with only exogenous ATP was not inhibited by the ryanodine receptor blockers tetracaine or ruthenium red. However, the SR Ca2+-ATPase (SERCA) inhibitors cyclopiazonic acid or 2,5-di(tert-butyl)-1,4-benzohydroquinone significantly decreased Ca2+ loss. At 100 nM external [Ca2+], the SR Ca2+ loss was also energy dependent and was not significantly inhibited by tetracaine. In cardiomyocytes, the decline in SR [Ca2+] at zero external [Ca2+] was almost two times slower under optimal energetic conditions than in the presence of exogenous ATP only.

Conclusion: At low extra-reticular [Ca2+], the main leak pathway is an energy-sensitive backward Ca2+ pump, and direct mitochondrial-SERCA ATP channelling is more effective in leak prevention than local ATP generation by bound CK.

KEYWORDS Energy metabolism; Sarcoplasmic reticulum; Calcium homeostasis; Mitochondria; Creatine kinase

Time for primary review: 20 days


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




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.