ArticleHeart rhythm2014
KCNJ2 mutation causes an adrenergic-dependent rectification abnormality with calcium sensitivity and ventricular arrhythmia.
Article in Heart rhythm, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- A new approach methodology for studying intrinsic ventricular arrhythmias in Fabry disease.Frontiers in cardiovascular medicine · 2026Article
- Methadone Blockade of Inward Rectifier Potassium Current Promotes Both Early and Delayed Repolarization Arrhythmias: Mechanistic Insights From Computational Modeling.Journal of the American Heart Association · 2025Article
- Atomic-level investigation of KCNJ2 mutations associated with ventricular arrhythmic syndrome phenotypes.Scientific reports · 2025Article
- Beta-Adrenergic Activation of the Inward Rectifier KInternational journal of molecular sciences · 2024Article
- The network of cardiac KNaunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil syndrome.Cardiovascular research · 2023Article
- Tetramisole is a new IPharmacology research & perspectives · 2022Review
- Arrhythmogenesis and Prolonged Repolarization From Synthetic Opioids: Finally Sorted?Journal of the American Heart Association · 2022Article
- Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death.European heart journal · 2022Article
- Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population.Biomedicines · 2022Review
- Proteomic Analysis of the Functional Inward Rectifier Potassium Channel (Kir) 2.1 Reveals Several Novel Phosphorylation Sites.Biochemistry · 2021Article
- "Ryanopathies" and RyR2 dysfunctions: can we further decipher them using in vitro human disease models?Cell death & disease · 2021Review
- Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: A Translational Perspective for the Clinician-Scientist.International journal of molecular sciences · 2021Review
- Cardiac potassium inward rectifier Kir2: Review of structure, regulation, pharmacology, and arrhythmogenesis.Heart rhythm · 2021Review
- Characterization of Loss-Of-FunctionFrontiers in genetics · 2021Article
- Post-mortem genetic investigation of cardiac disease-associated genes in sudden infant death syndrome (SIDS) cases.International journal of legal medicine · 2021Article
- Genetic Loss ofCirculation. Arrhythmia and electrophysiology · 2020Article
- Andersen-Tawil Syndrome Is Associated With Impaired PIPFrontiers in pharmacology · 2020Article
- Asymptomatic ventricular tachycardia: diagnostic pitfalls of Andersen-Tawil syndrome-a case report.European heart journal. Case reports · 2018Article
- Flecainide treats a novelHeartRhythm case reports · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundKCNJ2 mutations are associated with a variety of inherited arrhythmia syndromes including catecholaminergic polymorphic ventricular tachycardia 3.
objectiveTo characterize the detailed cellular mechanisms of the clinically recognized KCNJ2 mutation R67Q.
methodsKir2.1 current density was measured from COS-1 cells transiently transfected with wild-type human Kir-2.1 (WT-Kir2.1) and/or a heterozygous missense mutation in KCNJ2 (R67Q-Kir2.1) by using the whole-cell voltage clamp technique. Catecholamine activity was simulated with protein kinase A-stimulating cocktail exposure. Phosphorylation-deficient mutants, S425N-Kir2.1 and S425N-Kir2.1/R67Q-S425N-Kir2.1, were used in a separate set of experiments. HA- or Myc-Tag-WT-Kir2.1 and HA-Tag-R67Q-Kir2.1 were used for confocal imaging.
resultsA 33-year-old woman presented with a catecholaminergic polymorphic ventricular tachycardia-like clinical phenotype and was found to have KCNJ2 missense mutation R67Q. Treatment with nadolol and flecainide resulted in the complete suppression of arrhythmias and symptom resolution. Under baseline conditions, R67Q-Kir2.1 expressed alone did not produce inward rectifier current while cells coexpressing WT-Kir2.1 and R67Q-Kir2.1 demonstrated the rectification index (RI) similar to that of WT-Kir2.1. After PKA stimulation, R67Q-Kir2.1/WT-Kir2.1 failed to increase peak outward current density; WT-Kir2.1 increased by 46% (n = 5), while R67Q-Kir2.1/WT-Kir2.1 decreased by 6% (n = 6) (P = .002). Rectification properties in R67Q-Kir2.1/WT-Kir2.1 demonstrated sensitivity to calcium with a decreased RI in the high-calcium pipette solution (RI 20.3% ± 4.1%) than in the low-calcium pipette solution (RI 36.5% ± 5.7%) (P < .05). Immunostaining of WT-Kir2.1 and R67Q-Kir2.1 individually and together showed a normal membrane expression pattern and colocalization by using the Pearson correlation coefficient.
conclusionsR67Q-Kir2.1 is associated with an adrenergic-dependent clinical and cellular phenotype with rectification abnormality enhanced by increased calcium. These findings are a significant advancement of our knowledge and understanding of the phenotype-genotype relationship of arrhythmia syndromes related to KCNJ2 mutations.
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