Dataset Information

Dopamine D1/D5 Receptor Signaling Is Involved in Arrhythmogenesis in the Setting of Takotsubo Cardiomyopathy.

ABSTRACT:

Background

Previous 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.

Methods

Human-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.

Results

High 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 I_Kr channels.

Conclusions

Dopamine 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.

SUBMITTER: Huang M

PROVIDER: S-EPMC8855058 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dopamine D1/D5 Receptor Signaling Is Involved in Arrhythmogenesis in the Setting of Takotsubo Cardiomyopathy.

Huang Mengying M Yang Zhen Z Li Yingrui Y Lan Huan H Cyganek Lukas L Yuecel Goekhan G Lang Siegfried S Bieback Karen K El-Battrawy Ibrahim I Zhou Xiaobo X Borggrefe Martin M Akin Ibrahim I

Frontiers in cardiovascular medicine 20220204

<h4>Background</h4>Previous 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.<h4>Methods</h4>Human-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 ...[more]

PMID: 35187102

Similar Datasets

Project description:BACKGROUND: Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. OBJECTIVE: This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. DATA SOURCES: A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. REVIEW METHODS: The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. RESULTS: Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203-214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027-1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858-865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472-479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. CONCLUSION: Whether an emotional or physical event precedes one's symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical community.

Dataset Information

Dopamine D1/D5 Receptor Signaling Is Involved in Arrhythmogenesis in the Setting of Takotsubo Cardiomyopathy.

Background

Methods

Results

Conclusions

Publications

Dopamine D1/D5 Receptor Signaling Is Involved in Arrhythmogenesis in the Setting of Takotsubo Cardiomyopathy.

Similar Datasets

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