ArticleCirculation research2009
Oxidative-stress-induced afterdepolarizations and calmodulin kinase II signaling.
Article in Circulation research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 1 of them a synthesis that pooled it.
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Who cites it
166 citing papers in PubMed, 1 synthesis or guideline pooled it, 265 citations in OpenAlex.
- Oxygen therapy for acute myocardial infarction.The Cochrane database of systematic reviews · 2016Pooled it
- Prognostic Relevance of Nonsustained Ventricular Tachycardia in Patients with Pulmonary Hypertension.BioMed research international · 2016Trial
- A Computational Model of Oxidative Stress in a Human Ventricular Myocyte.bioRxiv : the preprint server for biology · 2026Article
- Review
- Is anaemia associated with QTc prolongation? A retrospective cross-sectional analysis from a rural population-based cohort.BMJ open · 2025Observational
- CDR1as modulates arrhythmia post-myocardial infarction via regulating Cav1.2.Acta biochimica et biophysica Sinica · 2025Article
- Redox imbalance and oxidative stress in cardiovascular diseases: mechanisms, biomarkers, and therapeutic targets.Archives of medical sciences. Atherosclerotic diseases · 2025Article
- Role of ryanodine receptor cooperativity in CaThe Journal of physiology · 2024Article
- A Mitochondrial Basis for Heart Failure Progression.Cardiovascular drugs and therapy · 2024Review
- Modeling cardiomyocyte signaling and metabolism predicts genotype-to-phenotype mechanisms in hypertrophic cardiomyopathy.Computers in biology and medicine · 2024Article
- Cardiac monoamine oxidase-A inhibition protects against catecholamine-induced ventricular arrhythmias via enhanced diastolic calcium control.Cardiovascular research · 2024Article
- Hourly air pollution exposure and the onset of symptomatic arrhythmia: an individual-level case-crossover study in 322 Chinese cities.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023Article
- Acute Impact of Fine Particulate Air Pollution on Cardiac Arrhythmias in a Population-Based Sample of Adolescents: The Penn State Child Cohort.Journal of the American Heart Association · 2022Article
- Review
- Analysis of Therapeutic Targets of A Novel Peptide Athycaltide-1 in the Treatment of Isoproterenol-Induced Pathological Myocardial Hypertrophy.Cardiovascular therapeutics · 2022Article
- Multiscale Modeling of the Mitochondrial Origin of Cardiac Reentrant and Fibrillatory Arrhythmias.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Ageing Increases Cardiac Electrical Remodelling in Rats and Mice via NOX4/ROS/CaMKII-Mediated Calcium Signalling.Oxidative medicine and cellular longevity · 2022Article
- Targeting late ICaL to close the window to ventricular arrhythmias.The Journal of general physiology · 2021Article
- Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current.The Journal of general physiology · 2021Article
- Cardiomyocyte NaBasic research in cardiology · 2021Article
106 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
In the heart, oxidative stress caused by exogenous H(2)O(2) has been shown to induce early afterdepolarizations (EADs) and triggered activity by impairing Na current (I(Na)) inactivation. Because H(2)O(2) activates Ca(2+)/calmodulin kinase (CaMK)II, which also impairs I(Na) inactivation and promotes EADs, we hypothesized that CaMKII activation may be an important factor in EADs caused by oxidative stress. Using the patch-clamp and intracellular Ca (Ca(i)) imaging in Fluo-4 AM-loaded rabbit ventricular myocytes, we found that exposure to H(2)O(2) (0.2 to 1 mmol/L) for 5 to 15 minutes consistently induced EADs that were suppressed by the I(Na) blocker tetrodotoxin (10 micromol/L), as well as the I(Ca,L) blocker nifedipine. H(2)O(2) enhanced both peak and late I(Ca,L), consistent with CaMKII-mediated facilitation. By prolonging the action potential plateau and increasing Ca influx via I(Ca,L), H(2)O(2)-induced EADs were also frequently followed by DADs in response to spontaneous (ie, non-I(Ca,L)-gated) sarcoplasmic reticulum Ca release after repolarization. The CaMKII inhibitor KN-93 (1 micromol/L; n=4), but not its inactive analog KN-92 (1 micromol/L, n=5), prevented H(2)O(2)-induced EADs and DADs, and the selective CaMKII peptide inhibitor AIP (autocamtide-2-related inhibitory peptide) (2 micromol/L) significantly delayed their onset. In conclusion, H(2)O(2)-induced afterdepolarizations depend on both impaired I(Na) inactivation to reduce repolarization reserve and enhancement of I(Ca,L) to reverse repolarization, which are both facilitated by CaMKII activation. Our observations support a link between increased oxidative stress, CaMKII activation, and afterdepolarizations as triggers of lethal ventricular arrhythmias in diseased hearts.
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