ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Bradycardia alters Ca(2+) dynamics enhancing dispersion of repolarization and arrhythmia risk.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Ventricle-Specific Biomechanical Responses to Inotropic and Vasoactive Drugs in Human Myocardial Slices.Journal of cardiovascular translational research · 2026Article
- Reduction in atrial and ventricular electrical heterogeneity following pulmonary vein isolation in patients with atrial fibrillation.Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing · 2025Article
- An In Vivo Model of Estrogen Supplementation Concerning the Expression of CaJournal of cardiovascular development and disease · 2024Article
- Patient-specific induced pluripotent stem cell properties implicate CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- The role of P21-activated kinase (Pak1) in sinus node function.Journal of molecular and cellular cardiology · 2023Article
- High-rate pacing suppresses Torsade de Pointes arrhythmias and reduces spatial dispersion of repolarization in the chronic AV-block dog model.Frontiers in physiology · 2023Article
- Effect of C reactive protein on the sodium-calcium exchanger 1 in cardiomyocytes.Experimental and therapeutic medicine · 2021Article
- Thermal effects on cardiac alternans onset and development: A spatiotemporal correlation analysis.Physical review. E · 2021Article
- Severe Bradycardia Increases the Incidence and Severity of Torsade de Pointes Arrhythmias by Augmenting Preexistent Spatial Dispersion of Repolarization in the CAVB Dog Model.Frontiers in physiology · 2021Article
- Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction.Oxidative medicine and cellular longevity · 2021Review
- Canard analysis reveals why a large Ca2+ window current promotes early afterdepolarizations in cardiac myocytes.PLoS computational biology · 2020Article
- Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans.Frontiers in physiology · 2018Article
- Genomic upregulation of cardiac Cav1.2α and NCX1 by estrogen in women.Biology of sex differences · 2017Article
- QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology.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 · 2016Article
- The link between abnormal calcium handling and electrical instability in acquired long QT syndrome--Does calcium precipitate arrhythmic storms?Progress in biophysics and molecular biology · 2016Review
- Synchronous systolic subcellular Ca2+-elevations underlie ventricular arrhythmia in drug-induced long QT type 2.Circulation. Arrhythmia and electrophysiology · 2015Article
- Sympathetic nerve stimulation, not circulating norepinephrine, modulates T-peak to T-end interval by increasing global dispersion of repolarization.Circulation. Arrhythmia and electrophysiology · 2015Article
- Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium.American journal of physiology. Heart and circulatory physiology · 2014Article
- Sex differences in the mechanisms underlying long QT syndrome.American journal of physiology. Heart and circulatory physiology · 2014Review
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6 authors at 2 institutions in 1 country.
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Abstract
Bradycardia prolongs action potential (AP) durations (APD adaptation), enhances dispersion of repolarization (DOR), and promotes tachyarrhythmias. Yet, the mechanisms responsible for enhanced DOR and tachyarrhythmias remain largely unexplored. Ca(2+) transients and APs were measured optically from Langendorff rabbit hearts at high (150 × 150 μm(2)) or low (1.5 × 1.5 cm(2)) magnification while pacing at a physiological (120 beats/min) or a slow heart rate (SHR = 50 beats/min). Western blots and pharmacological interventions were used to elucidate the regional effects of bradycardia. As a result, bradycardia (SHR 50 beats/min) increased APDs gradually (time constant τf→s = 48 ± 9.2 s) and caused a secondary Ca(2+) release (SCR) from the sarcoplasmic reticulum during AP plateaus, occurring at the base on average of 184.4 ± 9.7 ms after the Ca(2+) transient upstroke. In subcellular imaging, SCRs were temporally synchronous and spatially homogeneous within myocytes. In diastole, SHR elicited variable asynchronous sarcoplasmic reticulum Ca(2+) release events leading to subcellular Ca(2+) waves, detectable only at high magnification. SCR was regionally heterogeneous, correlated with APD prolongation (P < 0.01, n = 5), enhanced DOR (r = 0.9277 ± 0.03, n = 7), and was gradually reversed by pacing at 120 beats/min along with APD shortening (P < 0.05, n = 5). A stabilizer of leaky ryanodine receptors (RyR2), 3-(4-benzylcyclohexyl)-1-(7-methoxy-2,3-dihydrobenzo[f][1,4]thiazepin-4(5H)-yl)propan-1-one (K201; 1 μM), suppressed SCR and reduced APD at the base, thereby reducing DOR (P < 0.02, n = 5). Ventricular ectopy induced by bradycardia (n = 5/15) was suppressed by K201. Western blot analysis revealed spatial differences of voltage-gated L-type Ca(2+) channel protein (Cav1.2α), Na(+)-Ca(2+) exchange (NCX1), voltage-gated Na(+) channel (Nav1.5), and rabbit ether-a-go-go-related (rERG) protein [but not RyR2 or sarcoplasmic reticulum Ca(2+) ATPase 2a] that correlate with the SCR distribution and explain the molecular basis for SCR heterogeneities. In conclusion, acute bradycardia elicits synchronized subcellular SCRs of sufficient magnitude to overcome the source-sink mismatch and to promote afterdepolarizations.
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