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Huang, Mengying [Verfasser:in]; Yang, Zhen [Verfasser:in]; Li, Yingrui [Verfasser:in]; Lan, Huan [Verfasser:in]; Cyganek, Lukas [Verfasser:in]; Yücel, Gökhan [Verfasser:in]; Lang, Siegfried [Verfasser:in]; Bieback, Karen [Verfasser:in]; El-Battrawy, Ibrahim [Verfasser:in]; Zhou, Xiao-Bo [Verfasser:in]; Borggrefe, Martin [Verfasser:in]; Akın, Ibrahim [Verfasser:in]

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

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  • Medientyp: E-Artikel
  • Titel: Dopamine D1/D5 receptor signaling is involved in arrhythmogenesis in the setting of takotsubo cardiomyopathy
  • Beteiligte: Huang, Mengying [Verfasser:in]; Yang, Zhen [Verfasser:in]; Li, Yingrui [Verfasser:in]; Lan, Huan [Verfasser:in]; Cyganek, Lukas [Verfasser:in]; Yücel, Gökhan [Verfasser:in]; Lang, Siegfried [Verfasser:in]; Bieback, Karen [Verfasser:in]; El-Battrawy, Ibrahim [Verfasser:in]; Zhou, Xiao-Bo [Verfasser:in]; Borggrefe, Martin [Verfasser:in]; Akın, Ibrahim [Verfasser:in]
  • Erschienen: 04 February 2022
  • Erschienen in: Frontiers in Cardiovascular Medicine ; 8(2022) vom: 4. Feb., Artikel-ID 777483, Seite 1-15
  • Sprache: Englisch
  • DOI: 10.3389/fcvm.2021.777463
  • Identifikator:
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.
  • Zugangsstatus: Freier Zugang