Fig. 5: A local heart clock drives time-of-day-dependent rhythms in cardiomyocyte excitability.
From: Distinct circadian mechanisms govern cardiac rhythms and susceptibility to arrhythmia
A Representative recordings of spontaneous atrial (pink) and ventricular (green) electrograms recorded in ex vivo Langendorff-perfused hearts collected from control (Bmal1Fl/Fl) and αMHCCREBmal1Fl/Fl mice at ZT0 or ZT12. B Interbeat interval showed a time-of-day (ZT0 blue, ZT12 black) difference in control but not αMHCCREBmal1Fl/Fl hearts; A–V conduction delay in isolated hearts did not vary by time of day (n = 7 hearts/group, two-way RM ANOVA, Sidak’s post hoc). C Representative multielectrode array recording of spontaneous action potential firing in primary cardiomyocytes. D, E Spontaneous firing rate in isolated cardiomyocytes showed robust circadian variation in constant culture conditions (D, n = 8, one-way RM ANOVA, Holm–Sidak post hoc), which followed rhythms of mPER2::LUC bioluminescence recorded in parallel cultures (RLU: relative light units, E). F Representative ventricular traces and pacing protocol (stimulation train shown below recording). Inset showing recovery to normal sinus rhythm (top) and induced ventricular tachycardia (VT; bottom). G Control hearts (n = 7/timepoint) showed a significant time-of-day susceptibility to VT (ZT0: 2 of 7 hearts tested, ZT12: 6 of 7; Chi-square), whereas only 1 of 14 αMHCCREBmal1Fl/Fl hearts (n = 7/timepoint) were susceptible. All data presented as mean ± SEM. *P < 0.05, **P < 0.01. Source data and statistical details are provided as a Source Data File.
