ArticleCirculation research2013
Unique cardiac Purkinje fiber transient outward current β-subunit composition: a potential molecular link to idiopathic ventricular fibrillation.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 93 citations in OpenAlex.
- The role of DPP6 dysregulation in neuropathology: from synaptic regulation to disease mechanisms.Frontiers in cellular neuroscience · 2025Review
- An hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.Stem cell research & therapy · 2024Article
- Review
- JCS/JHRS 2022 Guideline on Diagnosis and Risk Assessment of Arrhythmia.Journal of arrhythmia · 2024Article
- Management of patients with an electrical storm or clustered ventricular arrhythmias: a clinical consensus statement of the European Heart Rhythm Association of the ESC-endorsed by the Asia-Pacific Heart Rhythm Society, Heart Rhythm Society, and Latin-American Heart Rhythm Society.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 · 2024Article
- Outcomes in Dutch DPP6 risk haplotype for familial idiopathic ventricular fibrillation: a focused update.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2023Article
- Moderator Band and Ventricular Tachycardia: Structural or Functional Substrate?Journal of cardiovascular development and disease · 2023Review
- Prevalence of Mitral Annulus Disjunction and Mitral Valve Prolapse in Patients With Idiopathic Ventricular Fibrillation.Journal of the American Heart Association · 2022Article
- Catheter ablation of short-coupled variant of torsade de pointes.Clinical research in cardiology : official journal of the German Cardiac Society · 2022Article
- [24-year-old man with successful resuscitation due to ventricular fibrillation without evident cause].Herzschrittmachertherapie & Elektrophysiologie · 2021Article
- Rapid response to the alpha-1 adrenergic agent phenylephrine in the perioperative period is impacted by genomics and ancestry.The pharmacogenomics journal · 2021Article
- A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.Scientific reports · 2021Article
- Short-coupled premature ventricular beats leading to ventricular fibrillation in a young patient: A Sudden Arrhythmia Death Syndrome case report and literature review.HeartRhythm case reports · 2020Article
- Elective implantable cardioverter-defibrillator removal with extraction of leads following catheter ablation of idiopathic ventricular fibrillation and long-term surveillance.HeartRhythm case reports · 2020Article
- Epidemiology of inherited arrhythmias.Nature reviews. Cardiology · 2020Review
- Arrhythmias from the Right Ventricular Moderator Band: Diagnosis and Management.Arrhythmia & electrophysiology review · 2020Review
- Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study.Genes and immunity · 2020Article
- Transient outward KAmerican journal of physiology. Heart and circulatory physiology · 2019Article
- Emerging Roles of Neuronal CaFrontiers in molecular neuroscience · 2019Review
- The transient receptor potential melastatin 4 channel inhibitor 9-phenanthrol modulates cardiac sodium channel.British journal of pharmacology · 2018Article
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
rationaleA chromosomal haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation. The molecular basis of transient outward current (I(to)) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF I(to) and that its overexpression might specifically alter PF I(to) properties and repolarization.
objectiveTo assess the potential role of DPP6 in PF I(to). METHODS AND
resultsClinical data in 5 idiopathic ventricular fibrillation patients suggested arrhythmia origin in the PF-conducting system. PF and ventricular muscle I(to) had similar density, but PF I(to) differed from ventricular muscle in having tetraethylammonium sensitivity and slower recovery. DPP6 overexpression significantly increased, whereas DPP6 knockdown reduced, I(to) density and tetraethylammonium sensitivity in canine PF but not in ventricular muscle cells. The K(+)-channel interacting β-subunit K(+)-channel interacting protein type-2, essential for normal expression of I(to) in ventricular muscle, was weakly expressed in human PFs, whereas DPP6 and frequenin (neuronal calcium sensor-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary cells produced small I(to); I(to) amplitude was greatly enhanced by coexpression with K(+)-channel interacting protein type-2 or DPP6. Coexpression of DPP6 with Kv4.3 and K(+)-channel interacting protein type-2 failed to alter I(to) compared with Kv4.3/K(+)-channel interacting protein type-2 alone, but DPP6 expression with Kv4.3 and neuronal calcium sensor-1 (to mimic PF I(to) composition) greatly enhanced I(to) compared with Kv4.3/neuronal calcium sensor-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that I(to) enhancement can greatly accelerate PF repolarization.
conclusionsThese results point to a previously unknown central role of DPP6 in PF I(to), with DPP6 gain of function selectively enhancing PF current, and suggest that a DPP6-mediated PF early-repolarization syndrome might be a novel molecular paradigm for some forms of idiopathic ventricular fibrillation.
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