ArticleEuropean heart journal2015
Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1.
Article in European heart journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- The Dual Nature of Sinoatrial Node Remodelling in Athletes: A Systematic Review of Electrophysiological Adaptations and the Pathological Tipping Point.International journal of molecular sciences · 2025Pooled it
- Atropine-induced sinus tachycardia protects against exercise-induced ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2020Trial
- Calmodulin mutation N54I causes autosomal dominant CPVT in mice.bioRxiv : the preprint server for biology · 2026Article
- Small-conductance CaThe Journal of physiology · 2026Review
- Caveolar Compartmentalization of Pacemaker Signaling Ensures Stable Sinoatrial Rhythmicity Which Is Disrupted in Heart Failure.JACC. Clinical electrophysiology · 2026Article
- The emerging role of calsequestrin 2: from calcium sensor and modulator to arrhythmia driver.Journal of physiology and biochemistry · 2026Review
- Pharmacological Enhancement of Small Conductance CaCirculation research · 2025Article
- Relationship between stress hyperglycemia ratio and the incidence of atrial fibrillation in patients after coronary artery bypass grafting: a retrospective study based on the MIMIC-IV database.Diabetology & metabolic syndrome · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Sinoatrial node heterogeneity and fibroblasts increase atrial driving capability in a two-dimensional human computational model.Frontiers in physiology · 2024Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- PI3K(p110α) as a determinant and gene therapy for atrial enlargement in atrial fibrillation.Molecular and cellular biochemistry · 2023Review
- Article
- VDAC2 as a novel target for heart failure: CaCell calcium · 2022Review
- Effects of acute ischemia and hypoxia in young and adult calsequestrin (CSQ2) knock-out and wild-type mice.Molecular and cellular biochemistry · 2022Article
- Influence of sex on intracellular calcium homoeostasis in patients with atrial fibrillation.Cardiovascular research · 2022Article
- Slowing down as we age: aging of the cardiac pacemaker's neural control.GeroScience · 2022Review
- Cancer Chemotherapy-Induced Sinus Bradycardia: A Narrative Review of a Forgotten Adverse Effect of Cardiotoxicity.Drug safety · 2022Review
- The function and regulation of calsequestrin-2: implications in calcium-mediated arrhythmias.Biophysical reviews · 2022Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
aimsLoss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. METHODS AND
resultsIn vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca(2+) cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2(-/-)) mice. Casq2(-/-) mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca(2+) cycling, including abnormal Ca(2+) release, periods of significantly elevated diastolic Ca(2+) levels leading to pauses and unstable pacemaker rate. Importantly, Ca(2+) cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca(2+) transient upstrokes throughout the atrial pacemaker complex.
conclusionsLoss of CASQ2 causes abnormal sarcoplasmic reticulum Ca(2+) release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients.
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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.