Details der Publikation - Differential effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on cardiac Kv4.3 (Ito) channel isoforms

Differential effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on cardiac Kv4.3 (Ito) channel isoforms / Ann-Kathrin Rahm, Juline Hackbarth, Mara E. Müller, Julia Pfeiffer, Heike Gampp, Finn Petersenn, Rasmus Rivinius, Norbert Frey, Patrick Lugenbiel and Dierk Thomas

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 µM) blocked Kv4.3 L by 77 ± 2% and Kv4.3 S by 67 ± 6%, respectively. Metoprolol (100 µM) was less effective with inhibition of 37 ± 3% (Kv4.3 L) and 35 ± 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..

Medienart:	E-Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:24
Enthalten in:	International journal of molecular sciences - 24(2023), 18, Artikel-ID 13842, Seite 1-16

Sprache:	Englisch

Weiterer Titel:	Differential effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on cardiac K v 4.3 (I to) channel isoforms

Beteiligte Personen:	Rahm, Ann-Kathrin, 1988- [VerfasserIn] Hackbarth, Juline [VerfasserIn] Müller, Mara Elena [VerfasserIn] Pfeiffer, Julia [VerfasserIn] Gampp, Heike [VerfasserIn] Petersenn, Finn [VerfasserIn] Rivinius, Rasmus, 1986- [VerfasserIn] Frey, Norbert [VerfasserIn] Lugenbiel, Patrick, 1982- [VerfasserIn] Thomas, Dierk, 1974- [VerfasserIn]

Links:	Volltext [kostenfrei] Volltext [kostenfrei]

Themen:	Antiarrhythmic effects Betablocker Heart failure Ito Kv4.3

Anmerkungen:	Veröffentlicht: 8. September 2023 Gesehen am 21.11.2023 Im Titel sind der Buchstabe "v" und der Ausdruck "to" tiefgestellt

Umfang:	Illustrationen 16

doi:	10.3390/ijms241813842

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	187074523X

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Differential effects of the Betablockers Carvedilol, Metoprolol and Bisoprolol on cardiac Kv4.3 (Ito) channel isoforms / Ann-Kathrin Rahm, Juline Hackbarth, Mara E. Müller, Julia Pfeiffer, Heike Gampp, Finn Petersenn, Rasmus Rivinius, Norbert Frey, Patrick Lugenbiel and Dierk Thomas

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