ArticleThe Journal of physiology2002
Cytosolic Ca2+ triggers early afterdepolarizations and Torsade de Pointes in rabbit hearts with type 2 long QT syndrome.
Article in The Journal of physiology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Calcium and arrhythmogenesis.Physiological reviews · 2007Pooled it
- Distinct patterns of ventricular fibrillation onset in primary electrical diseases: insights from a retrospective multicentre registry.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 · 2025Article
- Beneficial action potential duration-shortening effects, but deleterious negative inotropism of IKs-activator docosahexaenoyl glycine in long QT syndrome type 2.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 · 2025Article
- Role of dynamical instability in QT interval variability and early afterdepolarization propensity.Biophysical journal · 2025Article
- Mechanism of Arrhythmogenesis Driven by Early After Depolarizations in Cardiac Tissue.PLoS computational biology · 2025Article
- Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.International journal of molecular sciences · 2024Review
- Curvature-mediated source and sink effects on the genesis of premature ventricular complexes in long QT syndrome.American journal of physiology. Heart and circulatory physiology · 2024Article
- Dissecting the roles of calcium cycling and its coupling with voltage in the genesis of early afterdepolarizations in cardiac myocyte models.PLoS computational biology · 2024Article
- p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.Nature cardiovascular research · 2023Article
- Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Initiation of ventricular arrhythmia in the acquired long QT syndrome.Cardiovascular research · 2023Article
- Molecular Changes in Cells of Patients with Type 2 Diabetes Mellitus Depending on Changes in Glycemia Level in the Context of Lifestyle-An Overview of the Latest Scientific Discoveries.Current issues in molecular biology · 2023Review
- Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria.Journal of clinical medicine · 2023Article
- Directed graph mapping shows rotors maintain non-terminating and focal sources maintain self-terminating Torsade de Pointes in canine model.Frontiers in physiology · 2023Article
- Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals.American journal of physiology. Heart and circulatory physiology · 2022Review
- Modeling Calcium Cycling in the Heart: Progress, Pitfalls, and Challenges.Biomolecules · 2022Review
- R-on-T and the initiation of reentry revisited: Integrating old and new concepts.Heart rhythm · 2022Article
- DG-Mapping: a novel software package for the analysis of any type of reentry and focal activation of simulated, experimental or clinical data of cardiac arrhythmia.Medical & biological engineering & computing · 2022Article
- Bifurcations and Proarrhythmic Behaviors in Cardiac Electrical Excitations.Biomolecules · 2022Review
- Targeting late ICaL to close the window to ventricular arrhythmias.The Journal of general physiology · 2021Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The role of intracellular Ca2+ (Ca2+i) in triggering early afterdepolarizations (EADs), the origins of EADs and the mechanisms underlying Torsade de Pointes (TdP) were investigated in a model of long QT syndrome (Type 2). Perfused rabbit hearts were stained with RH327 and Rhod-2/AM to simultaneously map membrane potential (V(m)) and Ca2+i with two photodiode arrays. The I(Kr) blocker E4031 (0.5 microM) together with 50 % reduction of [K+]o and [Mg2+]o elicited long action potentials (APs), V(m) oscillations on AP plateaux (EADs) then ventricular tachycardia (VT). Cryoablation of both ventricular chambers eliminated Purkinje fibres as sources of EADs. E4031 prolonged APs (0.28 to 2.3 s), reversed repolarization sequences (baseapex) and enhanced repolarization gradients (30 to 230 ms, n = 12) indicating a heterogeneous distribution of I(Kr). At low [K+]o and [Mg2+]o, E4031 elicited spontaneous Ca2+iand V(m) spikes or EADs (3.5 +/- 1.9 Hz) during the AP plateau (n = 6). EADs fired 'out-of-phase' from several sites, propagated, collided then evolved to TdP. Phase maps (Ca2+ivs. V(m)) had counterclockwise trajectories shaped like a 'boomerang' during an AP and like ellipses during EADs, with V(m) preceding Ca2+iby 9.2 +/- 1.4 (n = 6) and 7.2 +/- 0.6 ms (n = 5/6), respectively. After cryoablation, EADs from surviving epicardium (~1 mm) fired at the same frequency (3.4 +/- 0.35 Hz, n = 6) as controls. At the origins of EADs, Ca2+ipreceded V(m) and phase maps traced clockwise ellipses. Away from EAD origins, V(m) coincided with or preceded Ca2+i. In conclusion, overload elicits EADs originating from either ventricular or Purkinje fibres and 'out-of-phase' EAD activity from multiple sites generates TdP, evident in pseudo-ECGs.
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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.