Dopamine D1/D5 receptor signaling is involved in arrhythmogenesis in the setting of takotsubo cardiomyopathy

• Verfasst von: Huang, Mengying [VerfasserIn]
• Verfasst von: Yang, Zhen [VerfasserIn]
• Verfasst von: Li, Yingrui [VerfasserIn]
• Verfasst von: Lan, Huan [VerfasserIn]
• Verfasst von: Cyganek, Lukas [VerfasserIn]
• Verfasst von: Yücel, Gökhan [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: Borggrefe, Martin [VerfasserIn]
• Verfasst von: Akın, Ibrahim [VerfasserIn]
• Titel: Dopamine D1/D5 receptor signaling is involved in arrhythmogenesis in the setting of takotsubo cardiomyopathy
• Verf.angabe: Mengying Huang, Zhen Yang, Yingrui Li, Huan Lan, Lukas Cyganek, Goekhan Yuecel, Siegfried Lang, Karen Bieback, Ibrahim El-Battrawy, Xiaobo Zhou, Martin Borggrefe and Ibrahim Akin
• E-Jahr: 2022
• Jahr: 04 February 2022
• Umfang: 15 S.
• Fussnoten: Gesehen am 04.03.2022
• Titel Quelle: Enthalten in: Frontiers in Cardiovascular Medicine
• Ort Quelle: Lausanne : Frontiers Media, 2014
• Jahr Quelle: 2022
• Band/Heft Quelle: 8(2022) vom: 4. Feb., Artikel-ID 777483, Seite 1-15
• ISSN Quelle: 2297-055X
• DOI: doi:10.3389/fcvm.2021.777463
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1794696202
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

BackgroundPrevious studies suggested involvement of non-ß-adrenoceptors in the pathogenesis of Takotsubo cardiomyopathy (TTC). This study was designed to explore possible roles and underlying mechanisms of dopamine D1/D5 receptor coupled signaling in arrhythmogenesis of TTC.MethodsHuman-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were challenged by toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) for mimicking the catecholamine excess in setting of TTC. Specific receptor blockers and activators were used to unveil roles of D1/D5 receptors. Patch clamp, qPCR, and FACS analyses were performed in the study.ResultsHigh concentration Epi and two dopamine D1/D5 receptor agonists [(±)-SKF 38393 and fenoldopam] reduced the depolarization velocity and prolonged the duration of action potentials (APs) and caused arrhythmic events in iPSC-CMs, suggesting involvement of dopamine D1/D5 receptor signaling in arrhythmogenesis associated with QT interval prolongation in the setting of TTC. (±)-SKF 38393 and fenoldopam enhanced the reactive oxygen species (ROS)-production. H2O2 (100 μM) recapitulated the effects of (±)-SKF 38393 and fenoldopam on APs and a ROS-blocker N-acetylcysteine (NAC, 1 mM) abolished the effects, suggesting that the ROS-signaling is involved in the dopamine D1/D5 receptor actions. A NADPH oxidases blocker and a PKA- or PKC-blocker suppressed the effects of the dopamine receptor agonist, implying that PKA, NADPH oxidases and PKC participated in dopamine D1/D5 receptor signaling. The abnormal APs resulted from dopamine D1/D5 receptor activation-induced dysfunctions of ion channels including the Na+ and L-type Ca2+ and IKr channels.ConclusionsDopamine D1/D5 receptor signaling plays important roles for arrhythmogenesis of TTC. Dopamine D1/D5 receptor signaling in cardiomyocytes might be a potential target for treating arrhythmias in patients with TTC.