ArticleProceedings of the National Academy of Sciences of the United States of America2015
Burst pacemaker activity of the sinoatrial node in sodium-calcium exchanger knockout mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 86 citations in OpenAlex.
- Aging Disrupts L-type CaCirculation research · 2026Article
- Regulation of Pacemaker Current in the Sinoatrial Node by Zonula Occludens-1.bioRxiv : the preprint server for biology · 2026Article
- Caveolar Compartmentalization of Pacemaker Signaling Ensures Stable Sinoatrial Rhythmicity Which Is Disrupted in Heart Failure.JACC. Clinical electrophysiology · 2026Article
- L-Type CaCirculation research · 2026Article
- Regulation of Na/Ca exchange by cytoplasmic protons modifies intracellular calcium dynamics and the cardiac response to ischemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Review
- An In Vivo Model of Estrogen Supplementation Concerning the Expression of CaJournal of cardiovascular development and disease · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Article
- Intracellular ion accumulation in the genesis of complex action potential dynamics under cardiac diseases.Physical review. E · 2024Article
- Lipopolysaccharide-induced sepsis impairs M2R-GIRK signaling in the mouse sinoatrial node.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- What makes the sinoatrial node tick? A question not for the faint of heart.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- DeepMiceTL: a deep transfer learning based prediction of mice cardiac conduction diseases using early electrocardiograms.Briefings in bioinformatics · 2023Article
- Emergent activity, heterogeneity, and robustness in a calcium feedback model of the sinoatrial node.Biophysical journal · 2023Article
- Prolonged Piezo1 Activation Induces Cardiac Arrhythmia.International journal of molecular sciences · 2023Article
- Characterization of sinoatrial automaticity in Microcebus murinus to study the effect of aging on cardiac activity and the correlation with longevity.Scientific reports · 2023Article
- Reduction in Junctophilin 2 Expression in Cardiac Nodal Tissue Results in Intracellular Calcium-Driven Increase in Nodal Cell Automaticity.Circulation. Arrhythmia and electrophysiology · 2023Article
- POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.EMBO reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In sinoatrial node (SAN) cells, electrogenic sodium-calcium exchange (NCX) is the dominant calcium (Ca) efflux mechanism. However, the role of NCX in the generation of SAN automaticity is controversial. To investigate the contribution of NCX to pacemaking in the SAN, we performed optical voltage mapping and high-speed 2D laser scanning confocal microscopy (LSCM) of Ca dynamics in an ex vivo intact SAN/atrial tissue preparation from atrial-specific NCX knockout (KO) mice. These mice lack P waves on electrocardiograms, and isolated NCX KO SAN cells are quiescent. Voltage mapping revealed disorganized and arrhythmic depolarizations within the NCX KO SAN that failed to propagate into the atria. LSCM revealed intermittent bursts of Ca transients. Bursts were accompanied by rising diastolic Ca, culminating in long pauses dominated by Ca waves. The L-type Ca channel agonist BayK8644 reduced the rate of Ca transients and inhibited burst generation in the NCX KO SAN whereas the Ca buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (acetoxymethyl ester) (BAPTA AM) did the opposite. These results suggest that cellular Ca accumulation hinders spontaneous depolarization in the NCX KO SAN, possibly by inhibiting L-type Ca currents. The funny current (If) blocker ivabradine also suppressed NCX KO SAN automaticity. We conclude that pacemaker activity is present in the NCX KO SAN, generated by a mechanism that depends upon If. However, the absence of NCX-mediated depolarization in combination with impaired Ca efflux results in intermittent bursts of pacemaker activity, reminiscent of human sinus node dysfunction and "tachy-brady" syndrome.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.