ArticleCirculation. Arrhythmia and electrophysiology2009
Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in catecholaminergic polymorphic ventricular tachycardia.
Article in Circulation. Arrhythmia and electrophysiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 68 citations in OpenAlex.
- Beta-Adrenergic Activation of the Inward Rectifier KInternational journal of molecular sciences · 2024Article
- Identification of candidate biomarkers and pathways associated with type 1 diabetes mellitus using bioinformatics analysis.Scientific reports · 2022Article
- Proteomic Analysis of the Functional Inward Rectifier Potassium Channel (Kir) 2.1 Reveals Several Novel Phosphorylation Sites.Biochemistry · 2021Article
- Cardiac potassium inward rectifier Kir2: Review of structure, regulation, pharmacology, and arrhythmogenesis.Heart rhythm · 2021Review
- Advances in the Molecular Genetics of Catecholaminergic Polymorphic Ventricular Tachycardia.Frontiers in pharmacology · 2021Review
- Characterization of Loss-Of-FunctionFrontiers in genetics · 2021Article
- Inhibition of cardiac potassium currents by oxidation-activated protein kinase A contributes to early afterdepolarizations in the heart.American journal of physiology. Heart and circulatory physiology · 2020Article
- Genetic Loss ofCirculation. Arrhythmia and electrophysiology · 2020Article
- Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis.Royal Society open science · 2020Review
- Calcium Handling Defects and Cardiac Arrhythmia Syndromes.Frontiers in pharmacology · 2020Review
- Genetics and pharmacogenetics in the diagnosis and therapy of cardiovascular diseases.Acta bio-medica : Atenei Parmensis · 2019Review
- Altering integrin engagement regulates membrane localization of KJournal of cell science · 2019Article
- Identification of a novel exon3 deletion of RYR2 in a family with catecholaminergic polymorphic ventricular tachycardia.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2019Review
- Regulation of Kir2.1 Function Under Shear Stress and Cholesterol Loading.Journal of the American Heart Association · 2018Article
- Boosting the signal: Endothelial inward rectifier KMicrocirculation (New York, N.Y. : 1994) · 2017Review
- Flecainide treats a novelHeartRhythm case reports · 2017Article
- Review
- Current topics in catecholaminergic polymorphic ventricular tachycardia.Journal of arrhythmia · 2016Review
- A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia.Heart rhythm · 2016Article
- Maturing human pluripotent stem cell-derived cardiomyocytes in human engineered cardiac tissues.Advanced drug delivery reviews · 2016Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundKCNJ2 encodes Kir2.1, a pore-forming subunit of the cardiac inward rectifier current, I(K1). KCNJ2 mutations are associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia. The aim of this study was to characterize the biophysical and cellular phenotype of a KCNJ2 missense mutation, V227F, found in a patient with catecholaminergic polymorphic ventricular tachycardia. METHODS AND
resultsKir2.1-wild-type (WT) and V227F channels were expressed individually and together in Cos-1 cells to measure I(K1) by voltage clamp. Unlike typical Andersen-Tawil syndrome-associated KCNJ2 mutations, which show dominant negative loss of function, Kir2.1WT+V227F coexpression yielded I(K1) indistinguishable from Kir2.1-WT under basal conditions. To simulate catecholamine activity, a protein kinase A (PKA)-stimulating cocktail composed of forskolin and 3-isobutyl-1-methylxanthine was used to increase PKA activity. This PKA-simulated catecholaminergic stimulation caused marked reduction of outward I(K1) compared with Kir2.1-WT. PKA-induced reduction in I(K1) was eliminated by mutating the phosphorylation site at serine 425 (S425N).
conclusionsHeteromeric Kir2.1-V227F and WT channels showed an unusual latent loss of function biophysical phenotype that depended on PKA-dependent Kir2.1 phosphorylation. This biophysical phenotype, distinct from typical Andersen-Tawil syndrome mutations, suggests a specific mechanism for PKA-dependent I(K1) dysfunction for this KCNJ2 mutation, which correlates with adrenergic conditions underlying the clinical arrhythmia.
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