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Camera-based Measurements of Intracellular [Na+] in Murine Atrial Myocytes
Published on: May 27, 2022
Intracellular sodium elevation reprograms cardiac metabolism.
Dunja Aksentijević1,2, Anja Karlstaedt3, Marina V Basalay1
1School of Cardiovascular and Medical Sciences, British Heart Foundation Centre of Research Excellence, King's College London, The Rayne Institute, St Thomas' Hospital, London, UK.
Elevated intracellular sodium (Na) in the heart triggers metabolic changes, shifting energy use from fats to carbohydrates. Targeting sodium or mitochondrial exchangers may treat heart failure metabolic issues.
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Area of Science:
- Cardiovascular Physiology
- Cardiac Metabolism
- Molecular Cardiology
Background:
- Intracellular sodium (Na) elevation is a key feature of heart pathologies involving metabolic remodeling.
- Understanding the link between Na and metabolic changes is crucial for treating heart failure.
Purpose of the Study:
- To investigate if acute or chronic intracellular Na overload causally links to cardiac metabolic remodeling.
- To identify a common Na-mediated metabolic signature in the failing heart.
Main Methods:
- Utilized Langendorff-perfused mouse hearts (control, transgenic, ouabain-treated, hypertrophied).
- Employed multi-nuclear magnetic resonance spectroscopy (23Na, 31P, 13C NMR) and 1H-NMR metabolomic profiling.
- Performed in silico modeling of metabolic fluxes.
Main Results:
- Elevated intracellular Na induced adaptive metabolic alterations, including a shift from fatty acid to carbohydrate metabolism.
- Observed changes in glycolytic, anaplerotic, and Krebs cycle intermediate concentrations.
- Inhibition of the mitochondrial Na/Ca exchanger ameliorated these metabolic changes.
- In silico modeling revealed altered metabolic fluxes across multiple pathways.
Conclusions:
- Acute and chronic Na overload are causally linked to cardiac metabolic remodeling.
- A common Na-mediated metabolic fingerprint exists in the failing heart.
- Targeting Na overload or mitochondrial Na/Ca exchange may offer novel therapeutic strategies for heart failure.