ArticleEuropace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology2021
Effective termination of atrial fibrillation by SK channel inhibition is associated with a sudden organization of fibrillatory conduction.
Article in 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, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Inhibition of the KNature medicine · 2024Trial
- Prospective in silico trials identify combined SK and KThe Journal of physiology · 2026Article
- Computational modelling of the pro- and antiarrhythmic effects of atrial high rate-dependent trafficking of small-conductance calcium-activated potassium channels.The Journal of physiology · 2026Article
- Atrial arrhythmogenesis and electrophysiological remodeling in hypokalaemic metabolic syndrome: the role of apamin-sensitive SK channels.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 · 2025Article
- Cryo-EM structures of the small-conductance CaNature communications · 2025Article
- Activation of Small Conductance CaInternational journal of molecular sciences · 2025Article
- Evolution in electrophysiology 100 years after Einthoven: translational and computational innovations in rhythm control of atrial fibrillation.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 · 2024Review
- Analysis of drug-induced and spontaneous cardioversions reveals similar patterns leading to termination of atrial fibrillation.Frontiers in physiology · 2024Article
- From Atrial Small-conductance Calcium-activated Potassium Channels to New Antiarrhythmics.European cardiology · 2024Review
- Up-regulated small-conductance calcium-activated potassium currents contribute to atrial arrhythmogenesis in high-fat feeding mice.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 · 2023Article
- Dual effects of the small-conductance CaAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Recent Advances in Antiarrhythmic Drug Therapy.Drugs · 2023Review
- 25 years of basic and translational science in EP Europace: novel insights into arrhythmia mechanisms and therapeutic strategies.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 · 2023Review
- Enhanced CaCirculation research · 2023Article
- Channelopathy-causing mutations in the SCell calcium · 2022Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPharmacological termination of atrial fibrillation (AF) remains a challenge due to limited efficacy and potential ventricular proarrhythmic effects of antiarrhythmic drugs. SK channels are proposed as atrial-specific targets in the treatment of AF. Here, we investigated the effects of the new SK channel inhibitor AP14145. METHODS AND
resultsEight goats were implanted with pericardial electrodes for induction of AF (30 days). In an open-chest study, the atrial conduction velocity (CV) and effective refractory period (ERP) were measured during pacing. High-density mapping of both atrial free-walls was performed during AF and conduction properties were assessed. All measurements were performed at baseline and during AP14145 infusion [10 mg/kg/h (n = 1) or 20 mg/kg/h (n = 6)]. At an infusion rate of 20 mg/kg/h, AF terminated in five of six goats. AP14145 profoundly increased ERP and reduced CV during pacing. AP14145 increased spatiotemporal instability of conduction at short pacing cycle lengths. Atrial fibrillation cycle length and pathlength (AF cycle length × CV) underwent a strong dose-dependent prolongation. Conduction velocity during AF remained unchanged and conduction patterns remained complex until the last seconds before AF termination, during which a sudden and profound organization of fibrillatory conduction occurred.
conclusionAP14145 provided a successful therapy for termination of persistent AF in goats. During AF, AP14145 caused an ERP and AF cycle length prolongation. AP14145 slowed CV during fast pacing but did not lead to a further decrease during AF. Termination of AF was preceded by an abrupt organization of AF with a decline in the number of fibrillation waves.
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