Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
Toshihiro Yamaguchi, Tomokazu S. Sumida, Seitaro Nomura, Masahiro Satoh, Tomoaki Higo, Masamichi Ito, Toshiyuki Ko, Kanna Fujita, Mary Sweet, Atsushi Sanbe, Kenji Yoshimi, Ichiro Manabe, Toshikuni Sasaoka, Matthew R.G. Taylor, Haruhiro Toko, Eiki Takimoto, Atsuhiko T. Naito, Issei Komuro
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.