Fig. 6
From: Augmentation of myocardial If dysregulates calcium homeostasis and causes adverse cardiac remodeling
NCX blockade reverses HCN4-mediated changes of Ca2+ homeostasis. a Representative [Ca2+]i transient traces measured as change in the Fluo-4 fluorescence in electrically driven cardiomyocytes from wild type [baseline (gray) and ORM-10103-treated (orange)] and HCN4tg/wt [baseline (black) and ivabradine-treated (blue)] mice (3 months of age). b–f Quantitative analysis reveals changes in Ca2+ homeostasis of HCN4tg/wt cardiomyocytes that were extensively recovered by treatment with ORM-10103. Diastolic [Ca2+]I, markedly increased in HCN4tg/wt cardiomyocytes, was significantly lower after ORM-10103 treatment (TG vs. TG ORM; ***P < 0.001; ANOVA) (b). Similarly, total cellular Ca2+ movement (peak area) (TG vs. TG ORM; ***P < 0.001; ANOVA) (c), time to peak (TG vs. TG ORM; ***P < 0.001; ANOVA) (d) slope Ca2+ uptake ((TG vs. TG ORM; ***P < 0.001; ANOVA) (e), and time to half decay (D50) of calcium transients (TG vs. TG ORM; ***P < 0.001; ANOVA) (f), normalized to wild type levels after treatment of HCN4tg/wt cardiomyocytes with ORM-10103, indicating important implication of dysregulated NCX current in the changed Ca2+ homeostasis of HCN4tg/wt cardiomyocytes. Data are expressed as mean ± s.e.m. (wild type: n = 67 cells, HCN4tg/wt: n = 102 cells, ORM-treated wild type: n = 72 cells, ORM-treated HCN4tg/wt: n = 92 cells derived from six animals/group; *P < 0.05, **P < 0.01, ***P < 0.001 compared to wild type; ANOVA followed by Tukey test). Source data are provided as a Source data file
