Alpha 1-adrenoceptor signalling contributes to toxic effects of catecholamine on electrical properties in cardiomyocytes

• Verfasst von: Huang, Mengying [VerfasserIn]
• Verfasst von: Fan, Xuehui [VerfasserIn]
• Verfasst von: Yang, Zhen [VerfasserIn]
• Verfasst von: Cyganek, Lukas [VerfasserIn]
• Verfasst von: Li, Xin [VerfasserIn]
• Verfasst von: Yücel, Gökhan [VerfasserIn]
• Verfasst von: Lan, Huan [VerfasserIn]
• Verfasst von: Li, Yingrui [VerfasserIn]
• Verfasst von: Wendel, Angela [VerfasserIn]
• Verfasst von: Lang, Siegfried [VerfasserIn]
• Verfasst von: Bieback, Karen [VerfasserIn]
• Verfasst von: El-Battrawy, Ibrahim [VerfasserIn]
• Verfasst von: Zhou, Xiao-Bo [VerfasserIn]
• Verfasst von: Akın, Ibrahim [VerfasserIn]
• Verfasst von: Borggrefe, Martin [VerfasserIn]
• Titel: Alpha 1-adrenoceptor signalling contributes to toxic effects of catecholamine on electrical properties in cardiomyocytes
• Verf.angabe: Mengying Huang, Xuehui Fan, Zhen Yang, Lukas Cyganek, Xin Li, Goekhan Yuecel, Huan Lan, Yingrui Li, Angela Wendel, Siegfried Lang, Karen Bieback, Ibrahim El-Battrawy, Xiaobo Zhou, Ibrahim Akin and Martin Borggrefe
• E-Jahr: 2021
• Jahr: July 2021
• Umfang: 12 S.
• Fussnoten: Published: 19 January 2021 ; Gesehen am 24.06.2022
• Titel Quelle: Enthalten in: Europace
• Ort Quelle: Oxford : Oxford Univ. Press, 1999
• Jahr Quelle: 2021
• Band/Heft Quelle: 23(2021), 7 vom: Juli, Seite 1137-1148
• ISSN Quelle: 1532-2092
• DOI: doi:10.1093/europace/euab008
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1807807193

Abstract

This study aimed to investigate possible roles and underlying mechanisms of alpha-adrenoceptor coupled signalling for the pathogenesis of Takotsubo syndrome (TTS).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.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.