ArticleEBioMedicine2020
Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies.
Article in EBioMedicine, 2020. 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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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
21 citing papers in PubMed, 27 citations in OpenAlex.
- CaThe Journal of physiology · 2026Article
- Downregulation of L-type CaHeart rhythm · 2026Article
- Phosphoinositide Depletion and Compensatory Phospho-Signaling in Angiotensin II-Induced Heart Disease.Circulation research · 2026Article
- Stress-Induced calcium mishandling in cardiac (Patho)physiology.Cellular and molecular life sciences : CMLS · 2025Review
- Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.Channels (Austin, Tex.) · 2025Review
- Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling.Current heart failure reports · 2025Review
- Casein Kinase 2 Regulates the Intrinsic Activity of L-Type Calcium Currents in Cardiomyocytes.International journal of molecular sciences · 2025Article
- Molecular Mechanisms of L-Type Calcium Channel Dysregulation in Heart Failure.International journal of molecular sciences · 2025Review
- Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population.International journal of molecular sciences · 2025Article
- Neuro- and immuno-modulation mediated by the cardiac sympathetic nerve: a novel insight into the anti-ischemic efficacy of acupuncture.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Review
- Computational modeling of cardiac electrophysiology and arrhythmogenesis: toward clinical translation.Physiological reviews · 2024Review
- Diversity of cells and signals in the cardiovascular system.The Journal of physiology · 2023Article
- Regulation of cardiac function by cAMP nanodomains.Bioscience reports · 2023Review
- Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales.Biophysical reviews · 2021Review
- Review
- Mechanisms and Regulation of Cardiac CaInternational journal of molecular sciences · 2021Review
- Reconstitution of β-adrenergic regulation of CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Sympathetic Activation and Arrhythmogenesis after Myocardial Infarction: Where Do We Stand?Journal of cardiovascular development and disease · 2021Review
- Local hyperactivation of L-type CaScientific reports · 2021Article
- Nanoscale Organization, Regulation, and Dynamic Reorganization of Cardiac Calcium Channels.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSubcellular localization and function of L-type calcium channels (LTCCs) play an important role in regulating contraction of cardiomyocytes. Understanding how this is affected by the disruption of transverse tubules during heart failure could lead to new insights into the disease.
methodsCardiomyocytes were isolated from healthy donor hearts, as well as from patients with cardiomyopathies and with left ventricular assist devices. Scanning ion conductance and confocal microscopy was used to study membrane structures in the cells. Super-resolution scanning patch-clamp was used to examine LTCC function in different microdomains. Computational modeling predicted the impact of these changes to arrhythmogenesis at the whole-heart level.
findingsWe showed that loss of structural organization in failing myocytes leads to re-distribution of functional LTCCs from the T-tubules to the sarcolemma. In ischemic cardiomyopathy, the increased LTCC open probability in the T-tubules depends on the phosphorylation by protein kinase A, whereas in dilated cardiomyopathy, the increased LTCC opening probability in the sarcolemma results from enhanced phosphorylation by calcium-calmodulin kinase II. LVAD implantation corrected LTCCs pathophysiological activity, although it did not improve their distribution. Using computational modeling in a 3D anatomically-realistic human ventricular model, we showed how LTCC location and activity can trigger heart rhythm disorders of different severity.
interpretationOur findings demonstrate that LTCC redistribution and function differentiate between disease aetiologies. The subcellular changes observed in specific microdomains could be the consequence of the action of distinct protein kinases.
fundingThis work was supported by NIH grant (ROI-HL 126802 to NT-JG) and British Heart Foundation (grant RG/17/13/33173 to JG, project grant PG/16/17/32069 to RAC). Funders had no role in study design, data collection, data analysis, interpretation, writing of the report.
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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.