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 E., Sweet, Atsushi, Sanbe, Kenji, Yoshimi, Ichiro, Manabe, Toshikuni, Sasaoka, Matthew R.G., Taylor, Haruhiro, Toko, Eiki, Takimoto, Atsuhiko T., Naito, Issei, Komuro

Nature Communications |

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.