{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Bentzen BH"],"funding":["Horizon 2020","Innovationsfonden","Wellcome Trust"],"pagination":["610"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7232560"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11"],"pubmed_abstract":["<h4>Aims</h4>Small conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channels (SK channels, K<sub>Ca</sub>2) are a new target for treatment of atrial fibrillation (AF). AP30663 is a small molecule inhibitor of K<sub>Ca</sub>2 channels that is currently in clinical development for treatment of AF. The aim of this study is to present the electrophysiological profile and mechanism of action of AP30663 and its efficacy in prolonging atrial refractoriness in rodents, and by bioinformatic analysis investigate if genetic variants in <i>KCNN2</i> or <i>KCNN3</i> influence the expression level of these in human heart tissue.<h4>Methods and results</h4>Whole-cell and inside-out patch-clamp recordings of heterologously expressed K<sub>Ca</sub>2 channels revealed that AP30663 inhibits K<sub>Ca</sub>"],"journal":["Frontiers in pharmacology"],"pubmed_title":["Mechanisms of Action of the KCa2-Negative Modulator AP30663, a Novel Compound in Development for Treatment of Atrial Fibrillation in Man."],"pmcid":["PMC7232560"],"funding_grant_id":["100406/Z/12/Z"],"pubmed_authors":["Edvardsson N","Bentzen BH","Muthukumarasamy KM","Diness JG","Abildgaard L","Grunnet M","Sorensen US","Simo-Vicens R","Folkersen L","Speerschneider T","Bomholtz SH"],"additional_accession":[]},"is_claimable":false,"name":"Mechanisms of Action of the KCa2-Negative Modulator AP30663, a Novel Compound in Development for Treatment of Atrial Fibrillation in Man.","description":"<h4>Aims</h4>Small conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channels (SK channels, K<sub>Ca</sub>2) are a new target for treatment of atrial fibrillation (AF). AP30663 is a small molecule inhibitor of K<sub>Ca</sub>2 channels that is currently in clinical development for treatment of AF. The aim of this study is to present the electrophysiological profile and mechanism of action of AP30663 and its efficacy in prolonging atrial refractoriness in rodents, and by bioinformatic analysis investigate if genetic variants in <i>KCNN2</i> or <i>KCNN3</i> influence the expression level of these in human heart tissue.<h4>Methods and results</h4>Whole-cell and inside-out patch-clamp recordings of heterologously expressed K<sub>Ca</sub>2 channels revealed that AP30663 inhibits K<sub>Ca</sub>","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020","modification":"2026-05-01T13:50:04.058Z","creation":"2020-06-02T07:04:21Z"},"accession":"S-EPMC7232560","cross_references":{"pubmed":["32477117"],"doi":["10.3389/fphar.2020.00610"]}}