Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources - Institut d'Optique Graduate School Access content directly
Journal Articles Cardiovascular Research Year : 2009

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

Abstract

Time for primary review: 20 days Aims Increased diastolic sarcoplasmic reticulum (SR) Ca 2+ loss could depress contractility in heart failure. Since the failing myocardium has impaired energetics, we investigated whether Ca 2+ 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 Ca 2+-free solution. In ventricular fibres caffeine-induced tension transients under optimal energetic conditions were used to estimate SR [Ca 2+ ]. In cardiomyocytes, intra-SR Ca 2+ was monitored by use of the fluorescent marker Mag-fluo 4. In fibres, SR Ca 2+ 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 Ca 2+-ATPase (SERCA) inhibitors cyclopiazonic acid or 2,5-di(tert-butyl)-1,4-benzohydroquinone significantly decreased Ca 2+ loss. At 100 nM external [Ca 2+ ], the SR Ca 2+ loss was also energy dependent and was not significantly inhibited by tetracaine. In cardiomyocytes, the decline in SR [Ca 2+ ] at zero external [Ca 2+ ] was almost two times slower under optimal energetic conditions than in the presence of exogenous ATP only. Conclusion At low extra-reticular [Ca 2+ ], the main leak pathway is an energy-sensitive backward Ca 2+ pump, and direct mitochondrial-SERCA ATP channelling is more effective in leak prevention than local ATP generation by bound CK.
Fichier principal
Vignette du fichier
Kuum 2009 Cardiovasc Res.pdf (273.14 Ko) Télécharger le fichier
Origin Publication funded by an institution

Dates and versions

hal-04089168 , version 1 (04-05-2023)

Identifiers

Cite

Malle Kuum, Allen Kaasik, Frederic Joubert, Renée Ventura-Clapier, Vladimir Veksler. Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources. Cardiovascular Research, 2009, 83 (1), pp.89-96. ⟨10.1093/cvr/cvp125⟩. ⟨hal-04089168⟩
4 View
5 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More