ReviewFrontiers in pharmacology2014
CaMKII-dependent regulation of cardiac Na(+) homeostasis.
Review in Frontiers in pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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Who cites it
30 citing papers in PubMed.
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch.Frontiers in physiology · 2025Article
- Feedback contributions to excitation-contraction coupling in native functioning striated muscle.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Changes in cellular CaThe Journal of physiology · 2023Article
- Cardiac Remodelling Following Cancer Therapy: A Review.Cardiovascular toxicology · 2022Review
- Benefits of SGLT2 inhibitors in arrhythmias.Frontiers in cardiovascular medicine · 2022Review
- Late sodium current and calcium homeostasis in arrhythmogenesis.Channels (Austin, Tex.) · 2021Review
- Ca2+-dependent modulation of voltage-gated myocyte sodium channels.Biochemical Society transactions · 2021Review
- Cardioprotection by SGLT2 Inhibitors-Does It All Come Down to NaInternational journal of molecular sciences · 2021Review
- Arrhythmogenic and antiarrhythmic actions of late sustained sodium current in the adult human heart.Scientific reports · 2021Article
- Intracellular NaInternational journal of molecular sciences · 2021Article
- Phospho-ablation of cardiac sodium channel NaInternational journal of obesity (2005) · 2021Article
- Late Sodium Current Inhibitors as Potential Antiarrhythmic Agents.Frontiers in pharmacology · 2020Review
- Reduced cardiomyocyte NaJournal of cellular physiology · 2019Article
- Phosphorylation of cardiac voltage-gated sodium channel: Potential players with multiple dimensions.Acta physiologica (Oxford, England) · 2019Review
- Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the NaWiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- 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
- 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
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Na(+) homeostasis is a key regulator of cardiac excitation and contraction. The cardiac voltage-gated Na(+) channel, NaV1.5, critically controls cell excitability, and altered channel gating has been implicated in both inherited and acquired arrhythmias. Ca(2) (+)/calmodulin-dependent protein kinase II (CaMKII), a serine/threonine kinase important in cardiac physiology and disease, phosphorylates NaV1.5 at multiple sites within the first intracellular linker loop to regulate channel gating. Although CaMKII sites on the channel have been identified (S516, T594, S571), the relative role of each of these phospho-sites in channel gating properties remains unclear, whereby both loss-of-function (reduced availability) and gain-of-function (late Na(+) current, INa L) effects have been reported. Our review highlights investigating the complex multi-site phospho-regulation of NaV1.5 gating is crucial to understanding the genesis of acquired arrhythmias in heart failure (HF) and CaMKII activated conditions. In addition, the increased Na(+) influx accompanying INa L may also indirectly contribute to arrhythmia by promoting Ca(2) (+) overload. While the precise mechanisms of Na(+) loading during HF remain unclear, and quantitative analyses of the contribution of INa L are lacking, disrupted Na(+) homeostasis is a consistent feature of HF. Computational and experimental observations suggest that both increased diastolic Na(+) influx and action potential prolongation due to systolic INa L contribute to disruption of Ca(2) (+) handling in failing hearts. Furthermore, simulations reveal a synergistic interaction between perturbed Na(+) fluxes and CaMKII, and confirm recent experimental findings of an arrhythmogenic feedback loop, whereby CaMKII activation is at once a cause and a consequence of Na(+) loading.
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