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.

• Authors: Toshihiro Yamaguchi, Tomokazu S Sumida, Seitaro Nomura, Masahiro Satoh, Tomoaki Higo, Masamichi Ito, Toshiyuki Ko, Kanna Fujita, Mary E Sweet, Atsushi Sanbe, Kenji Yoshimi, Ichiro Manabe, Toshikuni Sasaoka, Matthew R G Taylor, Haruhiro Toko, Eiki Takimoto, Atsuhiko T Naito, Issei Komuro
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 4364 (08 31 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 32868781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DRD1 protein, human
• Receptors, Dopamine D1

Topics

• Animals
• Arrhythmias, Cardiac (etiology, prevention & control)
• Gene Expression Profiling (methods)
• Heart Failure
• Humans
• Mice
• Mice, Transgenic
• Myocytes, Cardiac (metabolism)
• Rats
• Receptors, Dopamine D1 (genetics, metabolism)
• Sequence Analysis, RNA (methods)
• Single-Cell Analysis (methods)
• Tachycardia, Ventricular (etiology, prevention & control)