{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T19:32:08Z","timestamp":1780083128315,"version":"3.54.0"},"reference-count":57,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heidelberg University Medical School Olympia-Morata"},{"name":"German Heart Foundation"},{"name":"Department of Cardiology"},{"name":"German Academic Scholarship Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac Kv4.3 channels contribute to the transient outward K+ current, Ito, during early repolarization of the cardiac action potential. Two different isoforms of Kv4.3 are present in the human ventricle and exhibit differential remodeling in heart failure (HF). Cardioselective betablockers are a cornerstone of HF with reduced ejection fraction therapy as well as ventricular arrhythmia treatment. In this study we examined pharmacological effects of betablockers on both Kv4.3 isoforms to explore their potential for isoform-specific therapy. Kv4.3 isoforms were expressed in Xenopus laevis oocytes and incubated with the respective betablockers. Dose-dependency and biophysical characteristics were examined. HEK 293T-cells were transfected with the two Kv4.3 isoforms and analyzed with Western blots. Carvedilol (100 \u00b5M) blocked Kv4.3 L by 77 \u00b1 2% and Kv4.3 S by 67 \u00b1 6%, respectively. Metoprolol (100 \u00b5M) was less effective with inhibition of 37 \u00b1 3% (Kv4.3 L) and 35 \u00b1 4% (Kv4.3 S). Bisoprolol showed no inhibitory effect. Current reduction was not caused by changes in Kv4.3 protein expression. Carvedilol inhibited Kv4.3 channels at physiologically relevant concentrations, affecting both isoforms. Metoprolol showed a weaker blocking effect and bisoprolol did not exert an effect on Kv4.3. Blockade of repolarizing Kv4.3 channels by carvedilol and metoprolol extend their pharmacological mechanism of action, potentially contributing beneficial antiarrhythmic effects in normal and failing hearts.<\/jats:p>","DOI":"10.3390\/ijms241813842","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T07:52:11Z","timestamp":1694159531000},"page":"13842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential Effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on Cardiac Kv4.3 (Ito) Channel Isoforms"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7509-887X","authenticated-orcid":false,"given":"Ann-Kathrin","family":"Rahm","sequence":"first","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juline","family":"Hackbarth","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara E.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Pfeiffer","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Gampp","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Petersenn","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1146-6319","authenticated-orcid":false,"given":"Rasmus","family":"Rivinius","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Lugenbiel","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dierk","family":"Thomas","sequence":"additional","affiliation":[{"name":"Heidelberg Center for Heart Rhythm Disorders, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Department of Cardiology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Heidelberg\/Mannheim, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1161\/01.RES.79.4.659","article-title":"Role of the Kv4.3 K+ channel in ventricular muscle. 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