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Updated: Jul 13, 2026
Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
Expression of SERCA isoform with faster Ca2+ transport properties improves postischemic cardiac function and Ca2+
M A Hassan Talukder1, Anuradha Kalyanasundaram, Xue Zhao
1Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
Insights
Introducing SERCA1a, a variant of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), significantly protects the heart against ischemia-reperfusion (I/R) injury by reducing intracellular calcium overload and preserving cardiac function.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Physiology
Background:
- Myocardial ischemia-reperfusion (I/R) injury causes significant heart damage, including contractile dysfunction and cell death.
- Intracellular calcium (Ca2+) overload, linked to reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity, is a key mechanism in I/R injury.
- Conflicting reports exist regarding SERCA inhibition versus upregulation for postischemic cardiac function.
Purpose of the Study:
- To investigate the protective effects of SERCA1a, a cardiac isoform with faster Ca2+ transport kinetics, against myocardial I/R injury.
- To evaluate whether SERCA1a expression improves postischemic cardiac function and myocardial salvage.
- To compare the outcomes in SERCA1a transgenic (SERCA1a(+/+)) and nontransgenic (NTG) mice.
Main Methods:
- Langendorff-perfused hearts from SERCA1a(+/+) and NTG mice underwent 30 minutes of global ischemia followed by reperfusion.
- In vivo regional I/R studies were also conducted.
- Measurements included contractile function, arrhythmias, myocardial structure, infarct size, and intracellular Ca2+ levels.
Main Results:
- SERCA1a(+/+) hearts exhibited enhanced baseline function and significantly improved postischemic contractile recovery (45 min) compared to NTG hearts.
- SERCA1a(+/+) hearts showed reduced arrhythmias, better-preserved myocardial structure, less infarction, and improved ultrastructure.
- Intraischemic Ca2+ levels were notably lower in SERCA1a(+/+) hearts, and in vivo studies confirmed reduced infarct size.
Conclusions:
- SERCA1a expression provides significant cardioprotection against I/R injury.
- This protection is mediated by reduced postischemic intracellular Ca2+ overload.
- SERCA1a represents a potential therapeutic target for mitigating myocardial I/R damage.
Abstract:
Myocardial ischemia-reperfusion (I/R) injury is associated with contractile dysfunction, arrhythmias, and myocyte death. Intracellular Ca(2+) overload with reduced activity of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) is a critical mechanism of this injury. Although upregulation of SERCA function is well documented to improve postischemic cardiac function, there are conflicting reports where pharmacological inhibition of SERCA improved postischemic function. SERCA2a is the primary cardiac isoform regulating intracellular Ca(2+) homeostasis; however, SERCA1a has been shown to substitute SERCA2a with faster Ca(2+) transport kinetics. Therefore, to further address this issue and to evaluate whether SERCA1a expression could improve postischemic cardiac function and myocardial salvage, in vitro and in vivo myocardial I/R studies were performed on SERCA1a transgenic (SERCA1a(+/+)) and nontransgenic (NTG) mice. Langendorff-perfused hearts were subjected to 30 min of global ischemia followed by reperfusion. Baseline preischemic coronary flow and left ventricular developed pressure were significantly greater in SERCA1a(+/+) mice compared with NTG mice. Independent of reperfusion-induced oxidative stress, SERCA1a(+/+) hearts demonstrated greatly improved postischemic (45 min) contractile recovery with less persistent arrhythmias compared with NTG hearts. Morphometry showed better-preserved myocardial structure with less infarction, and electron microscopy demonstrated better-preserved myofibrillar and mitochondrial ultrastructure in SERCA1a(+/+) hearts. Importantly, intraischemic Ca(2+) levels were significantly lower in SERCA1a(+/+) hearts. The cardioprotective effect of SERCA1a was also observed during in vivo regional I/R with reduced myocardial infarct size after 24 h of reperfusion. Thus SERCA1a(+/+) hearts were markedly protected against I/R injury, suggesting that expression of SERCA 1a isoform reduces postischemic Ca(2+) overload and thus provides potent myocardial protection.
