Figure 5.

Ca²⁺ and late Na⁺ channel blockers rescued prolonged diastolic process in hypertrophic cardiomyopathy (HCM) induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) by re-balancing Ca²⁺ homeostasis in diseased cells. (A) Representative traces of Fura-2 AM Ca²⁺ imaging of Ctrl and HCM iPSC-CMs with and without Ca²⁺ and late Na⁺ blocker treatment. (B and C) Treatment by Ca²⁺ and late Na⁺ blocker significantly reduced diastolic Ca²⁺ concentration (B) and shortened Ca²⁺ transient decay duration (C). N > 27 cells in each groups. All groups were compared with untreated HCM iPSC-CMs by two-way ANOVA (Tukey method). (D–F) Using the sarcomere shortening assay, treatment by all three drugs retained the diastolic sarcomere length (D), increased relaxation rate (E), and reduced the normalized relaxation duration in HCM iPSC-CMs compared with untreated baseline (F). N > 28 cells for each groups. All groups were compared with untreated HCM iPSC-CMs by two-way ANOVA (Tukey method). For each group, data were generated from two different iPSC lines and three batches of differentiation.