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Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure.

ABSTRACT: Pathophysiological roles of cardiac dopamine system remain unknown. Here, we show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia. Comprehensive single-cell resolution analysis identifies the presence of D1R-expressing CMs in both heart failure model mice and in heart failure patients with sustained ventricular tachycardia. Overexpression of D1R in CMs disturbs normal calcium handling while CM-specific deletion of D1R ameliorates heart failure-associated ventricular arrhythmia. Thus, cardiac D1R has the potential to become a therapeutic target for preventing heart failure-associated ventricular arrhythmia.

SUBMITTER: Yamaguchi T

PROVIDER: S-EPMC7459304 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure.

Yamaguchi Toshihiro T Sumida Tomokazu S TS Nomura Seitaro S Satoh Masahiro M Higo Tomoaki T Ito Masamichi M Ko Toshiyuki T Fujita Kanna K Sweet Mary E ME Sanbe Atsushi A Yoshimi Kenji K Manabe Ichiro I Sasaoka Toshikuni T Taylor Matthew R G MRG Toko Haruhiro H Takimoto Eiki E Naito Atsuhiko T AT Komuro Issei I

Nature communications 20200831 1

Pathophysiological roles of cardiac dopamine system remain unknown. Here, we show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia. Comprehensive single-cell resolution analysis identifies the presence of D1R-expressing CMs in both heart failure model mice and in heart failure patients with sustained ventricular tachycardia. Overexpression of D1R in CMs disturbs normal calcium handling while CM-specific deletion ...[more]

PMID: 32868781

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