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08:29
Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Uncoupling protein-2 modulates myocardial excitation-contraction coupling
Jay D Turner1, Lawrence D Gaspers, Guoqiang Wang
1Department of Pharmacology and Physiology, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Circulation Research
|January 9, 2010
Summary
Uncoupling protein 2 (UCP2) in heart cells lowers mitochondrial membrane potential and impairs calcium handling, potentially worsening heart disease despite reducing oxidative stress.
Area of Science:
- Mitochondrial Physiology
- Cardiovascular Pathophysiology
- Cellular Bioenergetics
Background:
- Uncoupling protein 2 (UCP2) is a mitochondrial inner membrane protein found in mammalian myocardium.
- UCP2 is upregulated in conditions like heart failure and is thought to protect against oxidative stress.
- Conflicting roles proposed for UCP2, including dissipating mitochondrial proton gradient and facilitating mitochondrial calcium uptake.
Purpose of the Study:
- To investigate the role of myocardial UCP2 in cardiomyocyte bioenergetics.
- To examine the effects of UCP2 on calcium (Ca2+) homeostasis.
- To assess UCP2's impact on excitation-contraction coupling in neonatal cardiomyocytes.
Main Methods:
- Adenoviral-mediated UCP2 overexpression in neonatal cardiomyocytes.
- Measurement of mitochondrial membrane potential (ΔΨm) and oxygen consumption.
- Assessment of mitochondrial Ca2+ uptake using rhod-2 probe in permeabilized cells.
- Analysis of cytosolic Ca2+ transients and sparks using fluo-based probes and confocal microscopy.
Main Results:
- UCP2 overexpression mildly decreased ΔΨm and increased basal oxygen consumption without altering ATP levels.
- Marked inhibition of mitochondrial Ca2+ uptake observed with UCP2 overexpression.
- UCP2 overexpression prolonged cytosolic Ca2+ transient decay, increased Ca2+ spark activity, and promoted spark-wave propagation, indicating dysregulated excitation-contraction coupling.
Conclusions:
- While UCP2 lowers ΔΨm and may reduce oxidative stress, it negatively impacts beat-to-beat Ca2+ handling and excitation-contraction coupling.
- These detrimental effects on Ca2+ handling may contribute to the progression of heart disease.
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