ArticleCardiovascular research2016
Elevated local [Ca2+] and CaMKII promote spontaneous Ca2+ release in ankyrin-B-deficient hearts.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Meta-analysis of Transcriptomic Data Reveals Pathophysiological Modules Involved with Atrial Fibrillation.Molecular diagnosis & therapy · 2020Pooled it
- Heliox preconditioning exerts pulmonary protection effects on neonatal acute respiratory distress syndrome by inhibiting oxidative stress and apoptosis.Frontiers in pharmacology · 2025Article
- Reappraisal ofReviews in cardiovascular medicine · 2025Review
- Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites.Neuron · 2024Article
- Role of CaArchives of toxicology · 2023Review
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- Structures of PKA-phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy.eLife · 2022Article
- Impairment of μ-calpain activation by rhTNFR:Fc reduces severe burn-induced membrane disruption in the heart.Cell death discovery · 2022Article
- Mechanisms underlying the role of ankyrin-B in cardiac and neurological health and disease.Frontiers in cardiovascular medicine · 2022Review
- RIP3 Contributes to Cardiac Hypertrophy by Influencing MLKL-Mediated Calcium Influx.Oxidative medicine and cellular longevity · 2022Article
- Regulation of Cardiac Contractility by the Alpha 2 Subunit of the NaFrontiers in physiology · 2022Review
- Necrostatin-1 and necroptosis inhibition: Pathophysiology and therapeutic implications.Pharmacological research · 2021Review
- Ranolazine prevents pressure overload-induced cardiac hypertrophy and heart failure by restoring aberrant NaJournal of cellular physiology · 2019Article
- Ankyrin-B Q1283H Variant Linked to Arrhythmias Via Loss of Local Protein Phosphatase 2A Activity Causes Ryanodine Receptor Hyperphosphorylation.Circulation · 2018Article
- Inhibition of calcium/calmodulin-dependent kinase II restores contraction and relaxation in isolated cardiac muscle from type 2 diabetic rats.Cardiovascular diabetology · 2018Article
- [Inhibition of CaMKII alleviates myocardial ischemia?reperfusion injury by reducing mitochondrial oxidative stress in isolated perfused rat heart].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- Calcium-Mediated Oscillation in Membrane Potentials and Atrial-Triggered Activity in Atrial Cells of Casq2Frontiers in physiology · 2018Article
- Hypokalemia-Induced Arrhythmias and Heart Failure: New Insights and Implications for Therapy.Frontiers in physiology · 2018Review
- Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View.Frontiers in physiology · 2018Review
- The evolving role of ankyrin-B in cardiovascular disease.Heart rhythm · 2017Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
aimsLoss-of-function mutations in the cytoskeletal protein ankyrin-B (AnkB) cause ventricular tachyarrhythmias in humans. Previously, we found that a larger fraction of the sarcoplasmic reticulum (SR) Ca(2+) leak occurs through Ca(2+) sparks in AnkB-deficient (AnkB(+/-)) mice, which may contribute to arrhythmogenicity via Ca(2+) waves. Here, we investigated the mechanisms responsible for increased Ca(2+) spark frequency in AnkB(+/-) hearts. METHODS AND
resultsUsing immunoblots and phospho-specific antibodies, we found that phosphorylation of ryanodine receptors (RyRs) by CaMKII is enhanced in AnkB(+/-) hearts. In contrast, the PKA-mediated RyR phosphorylation was comparable in AnkB(+/-) and wild-type (WT) mice. CaMKII inhibition greatly reduced Ca(2+) spark frequency in myocytes from AnkB(+/-) mice but had little effect in the WT. Global activities of the major phosphatases PP1 and PP2A were similar in AnkB(+/-) and WT hearts, while CaMKII autophosphorylation, a marker of CaMKII activation, was increased in AnkB(+/-) hearts. Thus, CaMKII-dependent RyR hyperphosphorylation in AnkB(+/-) hearts is caused by augmented CaMKII activity. Intriguingly, CaMKII activation is limited to the sarcolemma-SR junctions since non-junctional CaMKII targets (phospholamban, HDAC4) are not hyperphosphorylated in AnkB(+/-) myocytes. This local CaMKII activation may be the consequence of elevated [Ca(2+)] in the junctional cleft caused by reduced Na(+)/Ca(2+) exchange activity. Indeed, using the RyR-targeted Ca(2+) sensor GCaMP2.2-FBKP12.6, we found that local junctional [Ca(2+)] is significantly elevated in AnkB(+/-) myocytes.
conclusionsThe increased incidence of pro-arrhythmogenic Ca(2+) sparks and waves in AnkB(+/-) hearts is due to enhanced CaMKII-mediated RyR phosphorylation, which is caused by higher junctional [Ca(2+)] and consequent local CaMKII activation.
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