Uncoupling Protein-2 Modulates Myocardial Excitation-Contraction Coupling

Rationale: Uncoupling protein (UCP)2 is a mitochondrial inner membrane protein that is expressed in mammalian myocardium under normal conditions and upregulated in pathological states such as heart failure. UCP2 is thought to protect cardiomyocytes against oxidative stress by dissipating the mitochondrial proton gradient and mitochondrial membrane potential (ΔΨm), thereby reducing mitochondrial reactive oxygen species generation. However, in apparent conflict with its uncoupling role, UCP2 has also been proposed to be essential for mitochondrial Ca2+ uptake, which could have a protective action by stimulating mitochondrial ATP production. Objective: The goal of this study was to better understand the role of myocardial UCP2 by examining the effects of UCP2 on bioenergetics, Ca2+ homeostasis, and excitation-contraction coupling in neonatal cardiomyocytes. Methods and Results: Adenoviral-mediated expression of UCP2 caused a mild depression of ΔΨm and increased the basal rate of oxygen consumption but did no...