Adrenergic receptor activation shapes circadian clock gene oscillations in HL-1 cardiomyocyte cell line

Circadian rhythms are physiological, biochemical and behavioural processes with a 24-h period molecularly regulated by clock genes. Cardiovascular physiology is subject to circadian variations in heart rate, blood pressure and contractility to optimize its function according to the rest-activity phases. Adrenergic receptors (ARs), activated by endogenous catecholamine hormones, are crucial in the regulation of cardiac functions; however, controllable in vitro models to study the intrinsic cardiomyocyte circadian clock with minimal systemic timing cues remain limited. Here, we use HL-1 cardiomyocyte cell line (HL-1 cells), in which serum shock induces synchronized oscillations of core clock gene transcripts compared with unsynchronized cultures. Different ARs activators onto HL-1 cells were applied under non-synchronized or synchronized conditions and circadian oscillation of representative clock genes was determined. We show that alpha- and beta-AR activation differentially modulates clock gene mesor, amplitude and phase. These findings support HL-1 cells as a convenient in vitro platform to investigate interactions between adrenergic signaling and cardiomyocyte clock gene oscillations.