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Updated: Mar 15, 2026
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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
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Cardiac Ryanodine Receptor (Ryr2)-mediated Calcium Signals Specifically Promote Glucose Oxidation via Pyruvate
Michael J Bround1,2, Rich Wambolt1,3, Haoning Cen1,2
1From the Cardiovascular Research Group, Life Sciences Institute and.
The Journal of Biological Chemistry
|September 14, 2016
Summary
Reduced cardiac ryanodine receptor (Ryr2) impairs heart metabolism. Partial Ryr2 loss disrupts mitochondrial calcium, decreasing glucose oxidation and increasing glycolysis, mimicking heart disease metabolic changes.
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Cardiac Metabolism
Background:
- Cardiac ryanodine receptor (Ryr2) dysfunction and metabolic alterations are hallmarks of heart disease.
- Previous studies suggest mitochondrial calcium (Ca2+) flux influences oxidative metabolism, but in vivo evidence is limited.
- The precise role of Ryr2 in regulating cardiomyocyte metabolism remains unclear.
Purpose of the Study:
- To investigate the in vivo role of Ryr2 in controlling cardiomyocyte metabolism and mitochondrial Ca2+ dynamics.
- To determine if partial Ryr2 reduction impacts cardiac function and substrate utilization.
- To elucidate the molecular mechanisms linking Ryr2 to metabolic regulation in the heart.
Main Methods:
- Generation and characterization of heart-specific, inducible Ryr2 haploinsufficient (cRyr2Δ50) mice.
- Assessment of cardiomyocyte Ca2+ signaling, contractility, and mitochondrial function.
- Analysis of cardiac substrate metabolism (glucose vs. fat oxidation) in perfused hearts.
- Comprehensive metabolomic, proteomic, and transcriptomic analyses.
Main Results:
- cRyr2Δ50 mice exhibited reduced cytosolic and mitochondrial Ca2+ transients without affecting cardiomyocyte contraction.
- Perfused hearts from cRyr2Δ50 mice showed decreased glucose oxidation and increased glycolysis, despite preserved contractile function.
- Pyruvate dehydrogenase, a key enzyme in glucose metabolism, was hyperphosphorylated and inhibited in cRyr2Δ50 hearts.
- Multi-omics analyses revealed altered metabolic networks associated with partial Ryr2 deficiency.
Conclusions:
- Ryr2 plays a critical role in regulating mitochondrial Ca2+ dynamics and promoting glucose oxidation in cardiomyocytes.
- Partial Ryr2 loss is sufficient to induce specific metabolic abnormalities observed in heart disease.
- Targeting Ryr2-mediated metabolic pathways may offer therapeutic strategies for heart conditions.
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