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Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers
Mark D. Levin, … , Jonathan A. Epstein, Vickas V. Patel
Mark D. Levin, … , Jonathan A. Epstein, Vickas V. Patel
Published October 12, 2009
Citation Information: J Clin Invest. 2009;119(11):3420-3436. https://doi.org/10.1172/JCI39109.
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Research Article Cardiology Article has an altmetric score of 10

Melanocyte-like cells in the heart and pulmonary veins contribute to atrial arrhythmia triggers

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Abstract

Atrial fibrillation is the most common clinical cardiac arrhythmia. It is often initiated by ectopic beats arising from the pulmonary veins and atrium, but the source and mechanism of these beats remains unclear. The melanin synthesis enzyme dopachrome tautomerase (DCT) is involved in intracellular calcium and reactive species regulation in melanocytes. Given that dysregulation of intracellular calcium and reactive species has been described in patients with atrial fibrillation, we investigated the role of DCT in this process. Here, we characterize a unique DCT-expressing cell population within murine and human hearts that populated the pulmonary veins, atria, and atrioventricular canal. Expression profiling demonstrated that this population expressed adrenergic and muscarinic receptors and displayed transcriptional profiles distinct from dermal melanocytes. Adult mice lacking DCT displayed normal cardiac development but an increased susceptibility to atrial arrhythmias. Cultured primary cardiac melanocyte-like cells were excitable, and those lacking DCT displayed prolonged repolarization with early afterdepolarizations. Furthermore, mice with mutations in the tyrosine kinase receptor Kit lacked cardiac melanocyte-like cells and did not develop atrial arrhythmias in the absence of DCT. These data suggest that dysfunction of melanocyte-like cells in the atrium and pulmonary veins may contribute to atrial arrhythmias.

Authors

Mark D. Levin, Min Min Lu, Nataliya B. Petrenko, Brian J. Hawkins, Tara H. Gupta, Deborah Lang, Peter T. Buckley, Jeanine Jochems, Fang Liu, Christopher F. Spurney, Li J. Yuan, Jason T. Jacobson, Christopher B. Brown, Li Huang, Friedrich Beermann, Kenneth B. Margulies, Muniswamy Madesh, James H. Eberwine, Jonathan A. Epstein, Vickas V. Patel

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Figure 6

Dct–/– mice have inducible and spontaneous atrial arrhythmias with normal cardiac structure and function.

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Dct–/– mice have inducible and spontaneous atrial arrhythmias with norm...
(A) Recordings from ECG lead I (I), right atrium, and right ventricle show AF induced by burst stimulation (S) in a Dct–/– animal. Irregularly irregular intervals between ventricular (v) beats are denoted. Sinus beats are shown on termination of the episode with normal atrial (a) and ventricular electrograms. Inset demonstrates magnified view of denoted area. (B) Real-time telemetry recorded in an awake Dct–/– mouse with an implantable monitor demonstrates spontaneous AF characterized by abrupt onset of a rapid irregularly irregular rhythm with no discrete p-waves. The inset shows a faster time scale of a few beats of sinus rhythm (arrows), followed by the onset of AF. (C) Surface ECGs from Dct–/– and Dct+/– littermate mice demonstrating normal ECG morphologies. (D) Two-dimensional echocardiographic imaging from a 4-chamber view demonstrating no qualitative difference in atrial dimensions during atrial systole or atrial diastole in Dct–/– and Dct+/+ littermate mice. Scale bar: 2 mm.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 2 clinical guideline sources
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