ArticleActa physiologica (Oxford, England)2008
Physiological consequences of the P2328S mutation in the ryanodine receptor (RyR2) gene in genetically modified murine hearts.
Article in Acta physiologica (Oxford, England), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Dual calcium-voltage optical mapping of regional voltage and calcium signals in intact murineJournal of molecular and cellular cardiology plus · 2024Article
- Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death.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 · 2023Article
- Cardiomyocyte electrophysiology and its modulation: current views and future prospects.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- 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
- 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
- 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
- Pro-arrhythmic atrial phenotypes in incrementally paced murine Pgc1βExperimental physiology · 2017Article
- Calcium Signaling and Cardiac Arrhythmias.Circulation research · 2017Review
- Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.Clinical and experimental pharmacology & physiology · 2017Article
- Murine Electrophysiological Models of Cardiac Arrhythmogenesis.Physiological reviews · 2017Review
- The RyR2-P2328S mutation downregulates Nav1.5 producing arrhythmic substrate in murine ventricles.Pflugers Archiv : European journal of physiology · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
aimTo explore the physiological consequences of the ryanodine receptor (RyR2)-P2328S mutation associated with catecholaminergic polymorphic ventricular tachycardia (CPVT).
methodsWe generated heterozygotic (RyR2 p/s) and homozygotic (RyR2 s/s) transgenic mice and studied Ca2+ signals from regularly stimulated, Fluo-3-loaded, cardiac myocytes. Results were compared with monophasic action potentials (MAPs) in Langendorff-perfused hearts under both regular and programmed electrical stimulation (PES).
resultsEvoked Ca2+ transients from wild-type (WT), heterozygote (RyR2 p/s) and homozygote (RyR2 s/s) myocytes had indistinguishable peak amplitudes with RyR2 s/s showing subsidiary events. Adding 100 nm isoproterenol produced both ectopic peaks and subsidiary events in WT but not RyR2 p/s and ectopic peaks and reduced amplitudes of evoked peaks in RyR2 s/s. Regularly stimulated WT, RyR2 p/s and RyR2 s/s hearts showed indistinguishable MAP durations and refractory periods. RyR2 p/s hearts showed non-sustained ventricular tachycardias (nsVTs) only with PES. Both nsVTs and sustained VTs (sVTs) occurred with regular stimuli and PES with isoproterenol treatment. RyR2 s/s hearts showed higher incidences of nsVTs before but mainly sVTs after introduction of isoproterenol with both regular stimuli and PES, particularly at higher pacing frequencies. Additionally, intrinsically beating RyR2 s/s showed extrasystolic events often followed by spontaneous sVT.
conclusionThe RyR2-P2328S mutation results in marked alterations in cellular Ca2+ homeostasis and arrhythmogenic properties resembling CPVT with greater effects in the homozygote than the heterozygote demonstrating an important gene dosage effect.
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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.