The cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a critical role in maintaining the intracellular calcium homeostasis during cardiac contraction and relaxation. It has been well documented over the years that altered expression and activity of SERCA2a can lead to systolic and diastolic dysfunction. The activity of SERCA2a is regulated by two structurally similar proteins, phospholamban (PLB) and sarcolipin (SLN). Although, the relevance of PLB has been extensively studied over the years, the role SLN in cardiac physiology is an emerging field of study. This review focuses on the advances in the understanding of the regulation of SERCA2a by SLN and PLB. In particular, it highlights the similarities and differences between the two proteins and their roles in cardiac patho-physiology.
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http://dx.doi.org/10.1016/j.yjmcc.2007.03.738 | DOI Listing |
Background: Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease where the most frequently associated mutations occur in the myosin-binding protein C () sarcomere-associated gene. HCM is also a common veterinary clinical problem in certain cat breeds such as Maine Coons and Ragdolls, also most associated with mutations in . Mouse models of HCM in which mutations are introduced recapitulate some, but not all, features of human HCM.
View Article and Find Full Text PDFPhysiol Rep
December 2024
Institute of Advanced Biomedical Engineering and Science, TWIns, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Cardiac alternans (C-ALT) is a phenomenon of alternating strong and weak contractions in the heart and is considered a risk factor for the development of heart failure and arrhythmias. However, no model has been reported that can induce C-ALT in vitro using human cells, and the developmental mechanism of C-ALT has not been studied using human cells. In this study, we successfully induced C-ALT in vitro using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
View Article and Find Full Text PDFCell Calcium
December 2024
Cardiac Signaling Center of USC, MUSC and Clemson University, 68 President St BEB 306, Charleston, SC 29425, USA. Electronic address:
Rationale & Methods: While signaling of cardiac SR by surface membrane proteins (I & I) is well studied, the regulation of mitochondrial Ca by plasmalemmal proteins remains less explored. Here we have examined the signaling of mitochondria and SR by surface-membrane calcium-transporting proteins, using genetically engineered targeted fluorescent probes, mito-GCamP6 and R-CEPIA1er.
Results: In voltage-clamped and TIRF-imaged cardiomyocytes, low Na induced SR Ca release was suppressed by short pre-exposures to ∼100 nM FCCP, suggesting mitochondrial Ca contribution to low Na triggered SR Carelease.
Br J Pharmacol
December 2024
Department of Pharmacology, University of California, Davis, Davis, California, USA.
Background And Purpose: Sarcoplasmic reticulum Ca-ATPase (SERCA2a) is impaired in heart failure. Phosphodiesterases (PDEs) are implicated in the modulation of local cAMP signals and protein kinase A (PKA) activity essential for cardiac function. We characterise PDE isoforms that underlie decreased activities of SERCA2a and reduced cardiac contractile function in diabetic cardiomyopathy.
View Article and Find Full Text PDFJ Gen Physiol
January 2025
Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Dilated cardiomyopathy (DCM) is a highly prevalent and genetically heterogeneous condition that results in decreased contractility and impaired cardiac function. The FK506-binding protein FKBP12 has been implicated in regulating the ryanodine receptor in skeletal muscle, but its role in cardiac muscle remains unclear. To define the effect of FKBP12 in cardiac function, we generated conditional mouse models of FKBP12 deficiency.
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