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Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
New perspectives on the role of SERCA2's Ca2+ affinity in cardiac function
P Vangheluwe1, K R Sipido, L Raeymaekers
1Laboratory of Physiology, University of Leuven, Herestraat 49, bus 802, B-3000 Leuven, Belgium. peter.vangheluwe@med.kuleuven.be
Biochimica Et Biophysica Acta
|September 29, 2006
Summary
Altered calcium affinity of the cardiac sarco(endo)plasmic reticulum Ca2+ transport ATPase (SERCA2a) can cause heart disease. Both reduced and increased affinity may lead to cardiac hypertrophy and dysfunction.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Cardiomyocyte relaxation and contraction depend on cardiac sarco(endo)plasmic reticulum (SR) Ca2+ transport ATPase (SERCA2a) activity.
- SERCA2a activity influences Ca2+ removal during relaxation, SR Ca2+ content, and subsequent Ca2+ release for contraction.
- Ca2+ affinity is a key determinant of SERCA2a activity within physiological Ca2+ ranges.
Purpose of the Study:
- To explore the role of SERCA2a Ca2+ affinity in cardiac function and disease.
- To investigate the consequences of altered Ca2+ affinity on cardiomyocyte contractility and SR Ca2+ handling.
- To examine the relationship between SERCA2a Ca2+ affinity and conditions like hypertrophic and dilated cardiomyopathy.
Main Methods:
- Analysis of SERCA2a function and Ca2+ affinity in various cardiac conditions.
- Investigating the impact of phospholamban and sarcolipin on SERCA2a Ca2+ affinity.
- Utilizing mouse and human models to study cardiomyopathy induced by altered SERCA2a affinity.
Main Results:
- Both chronically reduced and increased Ca2+ affinity of SERCA2a can impair cardiomyocyte SR Ca2+ handling and contractility.
- Reduced Ca2+ affinity is linked to depressed SR Ca2+ handling in heart failure.
- Increased Ca2+ affinity may also trigger cardiac hypertrophy, and some heart failure models show higher affinity.
- SERCA2a expression is vital for normal cardiac function and growth.
Conclusions:
- Imbalanced Ca2+ affinity of SERCA2a is a significant factor in the development of cardiomyopathies.
- Depressed SR Ca2+ uptake is not a universal characteristic of all heart failure.
- Fine-tuning SERCA2a Ca2+ affinity is crucial for maintaining cardiac health.
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