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

Copier la citation

Kuum, M., Kaasik, A., Joubert, F., Ventura-Clapier, R., & Veksler, V. (2009). Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources. Cardiovasc. Res., 83(1). https://doi.org/10.1093/cvr/cvp125

Copier la citation

@article{Kuum2009_75,
  author = {Kuum, Malle and Kaasik, Allen and Joubert, Frederic and Ventura-Clapier, Renee and Veksler, Vladimir},
  year = {2009},
  month = {7},
  title = {Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources},
  journal = {Cardiovasc. Res.},
  publisher = {OXFORD UNIV PRESS},
  volume = {83},
  number = {1},
  address = {GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND},
  abstract = {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\textbackslash{}\%-optimal energetic conditions; 27 +/- 5\textbackslash{}\%-exogenous ATP only, 52 +/- 5\textbackslash{}\%-endogenous CK activation; 88 +/- 8\textbackslash{}\%-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.},
  url = {http://www.dx.doi.org/10.1093/cvr/cvp125},
  doi = {10.1093/cvr/cvp125},
  issn = {0008-6363},
}

Copier la citation

TY  - JOUR
AU  - Kuum, Malle
AU  - Kaasik, Allen
AU  - Joubert, Frederic
AU  - Ventura-Clapier, Renee
AU  - Veksler, Vladimir
PY  - 2009
DA  - 2009/07/01
TI  - Energetic state is a strong regulator of sarcoplasmic reticulum Ca2+ loss in cardiac muscle: different efficiencies of different energy sources
JO  - Cardiovasc. Res.
VL  - 83
IS  - 1
PB  - OXFORD UNIV PRESS
SN  - 0008-6363
AB  - 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.
DO  - 10.1093/cvr/cvp125
UR  - http://www.dx.doi.org/10.1093/cvr/cvp125
ER  -