Alpha 1-adrenoceptor signalling contributes to toxic effects of catecholamine on electrical properties in cardiomyocytes
2021 | journal article. A publication with affiliation to the University of Göttingen.
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Alpha 1-adrenoceptor signalling contributes to toxic effects of catecholamine on electrical properties in cardiomyocytes
Huang, M.; Fan, X.; Yang, Z.; Cyganek, L. ; Li, X.; Yuecel, G. & Lan, H. et al. (2021)
Europace, 23(7) pp. 1137-1148. DOI: https://doi.org/10.1093/europace/euab008
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Details
- Authors
- Huang, Mengying; Fan, Xuehui; Yang, Zhen; Cyganek, Lukas ; Li, Xin; Yuecel, Goekhan; Lan, Huan; Li, Yingrui; Wendel, Angela; Lang, Siegfried; Borggrefe, Martin
- Abstract
- Abstract Aims This study aimed to investigate possible roles and underlying mechanisms of alpha-adrenoceptor coupled signalling for the pathogenesis of Takotsubo syndrome (TTS). Methods and results Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with a toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) to mimic the setting of TTS. Patch-clamp technique, polymerase chain reaction (PCR) and Fluorescence-activated cell sorting (FACS) were employed for the study. High concentration Epi suppressed the depolarization velocity, prolonged duration of action potentials and induced arrhythmic events in hiPSC-CMs. The Epi effects were attenuated by an alpha-adrenoceptor blocker (phentolamine), suggesting involvement of alpha-adrenoceptor signalling in arrhythmogenesis related to QT interval prolongation in the setting of TTS. An alpha 1-adrenoceptor agonist (phenylephrine) but not an alpha 2-adrenoceptor agonist (clonidine) mimicked Epi effects. Epi enhanced ROS production, which could be attenuated by the alpha- adrenoceptor blocker. Treatment of cells with H2O2 (100 µM) mimicked the effects of Epi on action potentials and a reactive oxygen species (ROS)-blocker (N-acetyl-I-cysteine, 1 mM) prevented the Epi effects, indicating that the ROS signalling is involved in the alpha-adrenoceptor actions. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidases were involved in alpha 1-adrenoceptor signalling. A protein kinase C (PKC) blocker suppressed the effects of Epi, phenylephrine and ROS as well, implying that PKC participated in alpha 1-adrenoceptor signalling and acted as a downstream factor of ROS. The abnormal action potentials resulted from alpha 1-adrenoceptor activation-induced dysfunctions of ion channels including the voltage-dependent Na+ and L-type Ca2+ channels. Conclusions Alpha 1-adrenoceptor signalling plays important roles for arrhythmogenesis of TTS. Alpha-adrenoceptor blockers might be clinically helpful for treating arrhythmias in patients with TTS.
- Issue Date
- 2021
- Journal
- Europace
- ISSN
- 1099-5129
- eISSN
- 1532-2092
- Language
- English