ArticleHeart rhythm2010
Novel KCNA5 mutation implicates tyrosine kinase signaling in human atrial fibrillation.
Article in Heart rhythm, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 84 citations in OpenAlex.
- Metabolic Remodeling and Mitochondrial Stress in Atrial Fibrillation: Mechanisms and Translational Targets.Reviews in cardiovascular medicine · 2025Review
- Oxidative stress and atrial fibrillation.Journal of molecular and cellular cardiology · 2024Review
- Genetic testing in early-onset atrial fibrillation.European heart journal · 2024Review
- Ubiquitination is involved in PKC-mediated degradation of cell surface Kv1.5 channels.The Journal of biological chemistry · 2024Article
- Review
- Pinocembrin ameliorates atrial fibrillation susceptibility in rats with anxiety disorder induced by empty bottle stimulation.Frontiers in pharmacology · 2022Article
- Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis:JACC. CardioOncology · 2021Review
- Pre-existing cardiovascular disease increases risk of atrial arrhythmia and mortality in cancer patients treated with Ibrutinib.Cardio-oncology (London, England) · 2021Article
- Genetics of atrial fibrillation-practical applications for clinical management: if not now, when and how?Cardiovascular research · 2021Review
- Disease Modeling and Disease Gene Discovery in Cardiomyopathies: A Molecular Study of Induced Pluripotent Stem Cell Generated Cardiomyocytes.International journal of molecular sciences · 2021Article
- Mechanical stretch increases Kv1.5 current through an interaction between the S1-S2 linker and N-terminus of the channel.The Journal of biological chemistry · 2020Article
- Ultrarapid Delayed Rectifier KFrontiers in cell and developmental biology · 2020Article
- Computational Study of the Loss-of-Function Mutations in the Kv1.5 Channel Associated with Atrial Fibrillation.ACS omega · 2018Article
- Rate-Dependent Role of IBiophysical journal · 2017Article
- Genistein and tyrphostin AG556 decrease ultra-rapidly activating delayed rectifier KBritish journal of pharmacology · 2017Article
- Lichen extracts regulate the expression of BMP7 via miR-194-5p targeting to decrease the risk atrial fibrillation.International journal of clinical and experimental pathology · 2017Article
- Genotype influence in responses to therapy for atrial fibrillation.Expert review of cardiovascular therapy · 2016Review
- Complex inheritance in Pulmonary Arterial Hypertension patients with several mutations.Scientific reports · 2016Article
- Cardiac Delayed Rectifier Potassium Channels in Health and Disease.Cardiac electrophysiology clinics · 2016Review
- Genetics of atrial fibrillation: from families to genomes.Journal of human genetics · 2016Review
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4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEmerging evidence has strongly implicated hereditary determinants for atrial fibrillation (AF). Loss-of-function mutations in KCNA5 encoding the ultrarapid delayed rectifier potassium current I(Kur) have been identified in AF families.
objectiveThe purpose of this study was to determine the clinical and biophysical phenotypes in a KCNA5 mutation with deletion of 11 amino acids in the N-terminus of the protein, which was identified in patients with lone AF.
methodsPatients with AF confirmed by ECG were prospectively enrolled in the Vanderbilt AF Registry, which comprises clinical and genetic databases. A KCNA5 mutation was generated by mutagenesis for electrophysiologic characterization.
resultsWe identified a novel 33-bp coding region deletion in two Caucasian probands. One proband was part of a kindred that included four other members with AF, and all were mutation carriers. The mutation results in deletion of 11 amino acids in the N-terminus of the protein, a proline-rich region as a binding site for Src homology 3 (SH3) domains associated with Src-family protein tyrosine kinase (TK) pathway. In transfected cells, the mutant caused approximately 60% decreased I(Kur) versus wild-type (WT) (75 +/- 8 pA/pF vs 180 +/- 15 pA/pF, P <.01) and dominant-negative effect on WT current (105 +/- 10 pA/pF, P <.01). Pretreatment with the Src inhibitor PP2 prevented v-Src TK from 90% suppressed WT current. In contrast, the mutant channel displayed no response to v-Src TK.
conclusionOur data implicate abnormal atrial repolarization control due to variable TK signaling as a mechanism in familial AF and thereby suggest a role for modulation of this pathway in AF and its treatment.
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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.