ArticleCardiovascular research2015
Ablation of HRC alleviates cardiac arrhythmia and improves abnormal Ca handling in CASQ2 knockout mice prone to CPVT.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
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- Induction of cardiac alternans in human iPS-derived cardiomyocytes through β-adrenergic receptor stimulation.Physiological reports · 2024Article
- Conditional ablation of MCU exacerbated cardiac pathology in a genetic arrhythmic model of CPVT.Journal of molecular and cellular cardiology plus · 2024Article
- The Structural-Functional Crosstalk of the Calsequestrin System: Insights and Pathological Implications.Biomolecules · 2023Review
- Article
- Oxidative DNA Damage-induced PARP-1-mediated Autophagic Flux Disruption Contributes to Bupivacaine-induced Neurotoxicity During Pregnancy.Current neuropharmacology · 2023Article
- Stress-driven cardiac calcium mishandling via a kinase-to-kinase crosstalk.Pflugers Archiv : European journal of physiology · 2021Review
- Phylogenetic and biochemical analysis of calsequestrin structure and association of its variants with cardiac disorders.Scientific reports · 2020Article
- Molecular and tissue mechanisms of catecholaminergic polymorphic ventricular tachycardia.The Journal of physiology · 2020Review
- Conditional Up-Regulation of SERCA2a Exacerbates RyR2-Dependent Ventricular and Atrial Arrhythmias.International journal of molecular sciences · 2020Article
- Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia.Journal of the American Heart Association · 2018Article
- Conditional ablation and conditional rescue models for Casq2 elucidate the role of development and of cell-type specific expression of Casq2 in the CPVT2 phenotype.Human molecular genetics · 2018Article
- The role of luminal Ca regulation in Ca signaling refractoriness and cardiac arrhythmogenesis.The Journal of general physiology · 2017Review
- Loss of MD1 exacerbates pressure overload-induced left ventricular structural and electrical remodelling.Scientific reports · 2017Article
- Characterization of Ca(2+)-Dependent Protein-Protein Interactions within the Ca(2+) Release Units of Cardiac Sarcoplasmic Reticulum.Molecules and cells · 2016Article
- The link between abnormalities of calcium handling proteins and catecholaminergic polymorphic ventricular tachycardia.Tzu chi medical journalReview
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsCardiac calsequestrin (CASQ2) and histidine-rich Ca-binding protein (HRC) are sarcoplasmic reticulum (SR) Ca-binding proteins that regulate SR Ca release in mammalian heart. Deletion of either CASQ2 or HRC results in relatively mild phenotypes characterized by preserved cardiac structure and function, although CASQ2 knockout (KO), or Cnull, shows increased arrhythmia burden under conditions of catecholaminergic stress. We hypothesized that given the apparent overlap of functions of CASQ2 and HRC, simultaneous ablation of both would deteriorate the cardiac phenotype compared with the single knockouts. METHODS AND
resultsIn contrast to this expectation, double knockout (DKO) mice lacking both CASQ2 and HRC exhibited normal cardiac ejection fraction and ultrastructure. Moreover, the predisposition to catecholamine-dependent arrhythmia that characterizes the Cnull phenotype was alleviated in the DKO mice. At the myocyte level, DKO mice displayed Ca transients of normal amplitude; additionally, the frequency of spontaneous Ca waves and sparks in the presence of isoproterenol were decreased markedly compared with Cnull. Furthermore, restitution of SR Ca release was slowed in DKO myocytes compared with Cnull cells.
conclusionOur results suggest that rather than being functionally redundant, CASQ2 and HRC modulate cardiac ryanodine receptor-mediated (RyR2) Ca release in an opposing manner. In particular, while CASQ2 stabilizes RyR2 rendering it refractory in the diastolic phase, HRC enhances RyR2 activity facilitating RyR2 recovery from refractoriness.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.