ArticleActa physiologica (Oxford, England)2015
Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts.
Article in Acta physiologica (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Pooled it
- Loose-patch clamp analysis applied to voltage-gated ionic currents following pharmacological ryanodine receptor modulation in murine hippocampal cornu ammonis-1 pyramidal neurons.Frontiers in physiology · 2024Article
- Cardiac arrhythmogenesis: roles of ion channels and their functional modification.Frontiers in physiology · 2024Review
- Advances in basic and translational research in atrial fibrillation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- How does flecainide impact RyR2 channel function?The Journal of general physiology · 2022Article
- Ca2+-dependent modulation of voltage-gated myocyte sodium channels.Biochemical Society transactions · 2021Review
- Article
- Is the Debate on the Flecainide Action on the RYR2 in CPVT Closed?Circulation research · 2021Article
- Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis.Scientific reports · 2020Article
- Conditional Up-Regulation of SERCA2a Exacerbates RyR2-Dependent Ventricular and Atrial Arrhythmias.International journal of molecular sciences · 2020Article
- Ion channel gating in cardiac ryanodine receptors from the arrhythmic RyR2-P2328S mouse.Journal of cell science · 2019Article
- Reduced cardiomyocyte NaJournal of cellular physiology · 2019Article
- Sodium current inhibition following stimulation of exchange protein directly activated by cyclic-3',5'-adenosine monophosphate (Epac) in murine skeletal muscle.Scientific reports · 2019Article
- Ventricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1βMechanisms of ageing and development · 2018Article
- Multiple targets for flecainide action: implications for cardiac arrhythmogenesis.British journal of pharmacology · 2018Review
- Epac-induced ryanodine receptor type 2 activation inhibits sodium currents in atrial and ventricular murine cardiomyocytes.Clinical and experimental pharmacology & physiology · 2018Article
- Cardiomyocyte ionic currents in intact young and aged murine Pgc-1βMechanisms of ageing and development · 2018Article
- Effects of ageing on pro-arrhythmic ventricular phenotypes in incrementally paced murine Pgc-1βPflugers Archiv : European journal of physiology · 2017Article
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
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8 authors at 2 institutions in 1 country.
Funding
Abstract
aimsCardiac ryanodine receptor mutations are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also predispose to atrial fibrillation. Recent work associates reduced atrial Nav 1.5 currents in homozygous RyR2-P2328S (RyR2(S/S) ) mice with slowed conduction and increased arrhythmogenicity. Yet clinically, and in murine models, the Nav 1.5 blocker flecainide reduces ventricular arrhythmogenicity in CPVT. We aimed to determine whether, and how, flecainide influences atrial arrhythmogenicity in RyR2(S/S) mice and their wild-type (WT) littermates.
methodsWe explored effects of 1 μm flecainide on WT and RyR2(S/S) atria. Arrhythmic incidence, action potential (AP) conduction velocity (CV), atrial effective refractory period (AERP) and AP wavelength (λ = CV × AERP) were measured using multi-electrode array recordings in Langendorff-perfused hearts; Na(+) currents (INa ) were recorded using loose patch clamping of superfused atria.
resultsRyR2(S/S) showed more frequent atrial arrhythmias, slower CV, reduced INa and unchanged AERP compared to WT. Flecainide was anti-arrhythmic in RyR2(S/S) but pro-arrhythmic in WT. It increased INa in RyR2(S/S) atria, whereas it reduced INa as expected in WT. It increased AERP while sparing CV in RyR2(S/S) , but reduced CV while sparing AERP in WT. Thus, RyR2(S/S) hearts have low λ relative to WT; flecainide then increases λ in RyR2(S/S) but decreases λ in WT.
conclusionsFlecainide (1 μm) rescues the RyR2-P2328S atrial arrhythmogenic phenotype by restoring compromised INa and λ, changes recently attributed to increased sarcoplasmic reticular Ca(2+) release. This contrasts with the increased arrhythmic incidence and reduced INa and λ with flecainide in WT.
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