ArticleCardiovascular research2016
Calmodulin/CaMKII inhibition improves intercellular communication and impulse propagation in the heart and is antiarrhythmic under conditions when fibrosis is absent.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Signal Recognition Granule Receptor Beta Subunit Promotes Arrhythmogenic Remodeling in the Heart Failure Mice.Journal of the American Heart Association · 2026Article
- Electrical Remodeling of Pressure Overloaded Rat Heart Is Attenuated if Imposed During Proliferative Cardiac Growth.Acta physiologica (Oxford, England) · 2025Article
- Atrial Fibrillation and Underlying Structural and Electrophysiological Heterogeneity.International journal of molecular sciences · 2024Review
- Integrative human atrial modelling unravels interactive protein kinase A and Ca2+/calmodulin-dependent protein kinase II signalling as key determinants of atrial arrhythmogenesis.Cardiovascular research · 2023Article
- Cellular mechanisms and molecular pathways linking bitter taste receptor signalling to cardiac inflammation, oxidative stress, arrhythmia and contractile dysfunction in heart diseases.Inflammopharmacology · 2023Review
- Regulatory mechanism of calcium/calmodulin-dependent protein kinase II in the occurrence and development of ventricular arrhythmia (Review).Experimental and therapeutic medicine · 2021Review
- RIPK3-Mediated Necroptosis in Diabetic Cardiomyopathy Requires CaMKII Activation.Oxidative medicine and cellular longevity · 2021Article
- Wenxin Keli for the Treatment of Arrhythmia-Systems Pharmacology andFrontiers in pharmacology · 2021Article
- A combined CaMKII inhibition and mineralocorticoid receptor antagonism via eplerenone inhibits functional deterioration in chronic pressure overloaded mice.Journal of cellular and molecular medicine · 2020Article
- "Heart Oddity": Intrinsically Reduced Excitability in the Right Ventricle Requires Compensation by Regionally Specific Stress Kinase Function.Frontiers in physiology · 2020Review
- Article
- Conduction in the right and left ventricle is differentially regulated by protein kinases and phosphatases: implications for arrhythmogenesis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the NaWiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- CaMKII blockade, cardiac conduction, and arrhythmia.Cardiovascular research · 2017Article
Corrections and comments
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21 authors.
Funding
Abstract
aimIn healthy hearts, ventricular gap junctions are mainly composed by connexin43 (Cx43) and localize in the intercalated disc, enabling appropriate electrical coupling. In diseased hearts, Cx43 is heterogeneously down-regulated, whereas activity of calmodulin/calcium-calmodulin protein kinase II (CaM/CaMKII) signalling increases. It is unclear if CaM/CaMKII affects Cx43 expression/localization or impulse propagation. We analysed different models to assess this. METHODS AND
resultsAC3-I mice with CaMKII genetically inhibited were subjected to pressure overload (16 weeks, TAC vs. sham). Optical and epicardial mapping was performed on Langendorff-perfused rabbit and AC3-I hearts, respectively. Cx43 subcellular distribution from rabbit/mouse ventricles was evaluated by immunoblot after Triton X-100-based fractionation. In mice with constitutively reduced CaMKII activity (AC3-I), conduction velocity (CV) was augmented (n = 11, P < 0.01 vs. WT); in AC3-I, CV was preserved after TAC, in contrast to a reduction seen in TAC-WT mice (-20%). Cx43 expression was preserved after TAC in AC3-I mice, though arrhythmias and fibrosis were still present. In rabbits, W7 (CaM inhibitor, 10 µM) increased CV (6-13%, n= 6, P< 0.05), while susceptibility to arrhythmias decreased. Immunoconfocal microscopy revealed enlarged Cx43 cluster sizes at intercalated discs of those hearts. Total Cx43 did not change by W7 (n= 4), whereas Triton X-100 insoluble Cx43 increased (+21%, n= 4, P< 0.01). Similar findings were obtained in AC3-I mouse hearts when compared with control, and in cultured dog cardiomyocytes. Functional implication was shown through increased intercellular coupling in cultured neonatal rat cardiomyocytes.
conclusionBoth acute and chronic CaM/CaMKII inhibition improves conduction characteristics and enhances localization of Cx43 in the intercalated disc. In the absence of fibrosis, this reduced the susceptibility for arrhythmias.
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