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. 2021 Oct 15;12:6035. doi: 10.1038/s41467-021-25942-4

Fig. 4. Ion fluxes facilitate circadian modulation of cardiomyocyte electrophysiology.

Fig. 4

a Abundance of selected ions and PER2::LUC reporter activity in primary cardiomyocytes (n = 4) under constant conditions. Values were normalized to maximal values in each timeseries. p values indicate comparison of damped cosine wave with straight-line fit (null hypothesis = no rhythm). b Cellular ion content of adult mouse heart tissue under diurnal conditions (n = 3, normalized to total protein). c Representative field potential traces of cardiomyocytes at peak or trough of ion rhythms and action potential frequency (representative biological replicate, mean signal from active electrodes is shown, n = 5, 11, 4, and 11, respectively). d Action potential frequency in primary cardiomyocytes at peak and trough of ion rhythms in the presence of the mTOR inhibitor torin1 (50 nM), and wash off from a representative biological replicate (mean values from active electrodes are presented, n = 12, 8, 13, and 9 for torin1 and 10, 3, 3, and 5 for wash off). e Heart rate (HR) measured ex vivo in Langendorff-perfused hearts from control and rapamycin-treated mice collected at ZT0 and ZT12 (n = 6 control ZT0, n = 8 control ZT12, n = 6 mTORC inhibition ZT0, n = 8 mTORC inhibition ZT12). f HR measured in vivo by telemetry in control (n = 6) or rapamycin-treated mice (n = 5) treated with metoprolol and atropine. Time-of-day variation in heart rate persists under complete autonomic blockade. Mean ± SEM shown throughout. Statistical tests are one-way ANOVA with Tukey’s MCT (b) and (c), Two-way ANOVA with Dunnett’s MCT (d), one-way ANOVA, and Sidak MCT (e), and mixed-effect analysis and Sidak MCT (f).