ArticleCirculation2015
Molecular Basis of Hypokalemia-Induced Ventricular Fibrillation.
Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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
49 citing papers in PubMed, 97 citations in OpenAlex.
- Trial
- Ventricular fibrillation triggered by recurrent hypoglycemia in a patient with insulinoma associated with MEN1: case report and review of literature.Endocrine journal · 2026Review
- Review
- Phase-targeting rapid cryofixation of the beating heart and histological analysis unveil contractile state-dependent sarcomere dynamics.Scientific reports · 2026Article
- Electrocardiographic Changes in Patients With Hypokalemia and Their Correlation With Serum Potassium Levels.Cureus · 2025Article
- NaInternational journal of cardiology. Heart & vasculature · 2025Article
- Mechanisms of torsades de pointes: an update.Frontiers in cardiovascular medicine · 2024Review
- In silico analysis of the dynamic regulation of cardiac electrophysiology by KThe Journal of physiology · 2023Article
- Prognosis of Older Adult Patients Suffering from Atrial Fibrillation and Hypokalemia.Clinical interventions in aging · 2023Article
- Association of Potassium Level at Discharge with Long-Term Mortality in Hospitalized Patients with Heart Failure.Journal of clinical medicine · 2022Article
- Association of Intravenous Potassium and Magnesium Administration With Spontaneous Conversion of Atrial Fibrillation and Atrial Flutter in the Emergency Department.JAMA network open · 2022Article
- Isolation and characterization of human embryonic stem cell-derived heart field-specific cardiomyocytes unravels new insights into their transcriptional and electrophysiological profiles.Cardiovascular research · 2022Article
- Review of the Pathophysiologic and Clinical Aspects of Hypokalemia in Children and Young Adults: an Update.Current treatment options in pediatrics · 2022Review
- The successful use of extracorporeal membrane oxygenation combined with continuous renal replacement therapy for a cardiac arrest patient with refractory hypokalemia and diabetic ketoacidosis.World journal of emergency medicine · 2022Article
- Regulation of Cardiac Contractility by the Alpha 2 Subunit of the NaFrontiers in physiology · 2022Review
- Suppression of ventricular arrhythmias by targeting late L-type Ca2+ current.The Journal of general physiology · 2021Article
- Effect of moderate potassium-elevating treatment in long QT syndrome: the TriQarr Potassium Study.Open heart · 2021Article
- Modelling sudden cardiac death risks factors in patients with coronavirus disease of 2019: the hydroxychloroquine and azithromycin case.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2021Article
- Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHypokalemia is known to promote ventricular arrhythmias, especially in combination with class III antiarrhythmic drugs like dofetilide. Here, we evaluated the underlying molecular mechanisms. METHODS AND
resultsArrhythmias were recorded in isolated rabbit and rat hearts or patch-clamped ventricular myocytes exposed to hypokalemia (1.0-3.5 mmol/L) in the absence or presence of dofetilide (1 μmol/L). Spontaneous early afterdepolarizations (EADs) and ventricular tachycardia/fibrillation occurred in 50% of hearts at 2.7 mmol/L [K] in the absence of dofetilide and 3.3 mmol/L [K] in its presence. Pretreatment with the Ca-calmodulin kinase II (CaMKII) inhibitor KN-93, but not its inactive analogue KN-92, abolished EADs and hypokalemia-induced ventricular tachycardia/fibrillation, as did the selective late Na current (INa) blocker GS-967. In intact hearts, moderate hypokalemia (2.7 mmol/L) significantly increased tissue CaMKII activity. Computer modeling revealed that EAD generation by hypokalemia (with or without dofetilide) required Na-K pump inhibition to induce intracellular Na and Ca overload with consequent CaMKII activation enhancing late INa and the L-type Ca current. K current suppression by hypokalemia and dofetilide alone in the absence of CaMKII activation were ineffective at causing EADs.
conclusionsWe conclude that Na-K pump inhibition by even moderate hypokalemia plays a critical role in promoting EAD-mediated arrhythmias by inducing a positive feedback cycle activating CaMKII and enhancing late INa. Class III antiarrhythmic drugs like dofetilide sensitize the heart to this positive feedback loop.
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What OpenQuestion holds
Registered trials
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.