Figure 9.

The effects of ryanodine on the [Ca²⁺]_i transients of control, CPVT1 and CPVT2 iPSC-CM. (A–C) [Ca²⁺]_i transients from the three groups demonstrating the effect of ryanodine. (D) [Ca⁺²]_i transient amplitude; (E) Diastolic [Ca²⁺]_i; (F) +d[Ca²⁺]_i/dt; (G) −d[Ca²⁺]_i/dt. Control iPSC-CM (n = 11), CPVT1 iPSC-CM (n = 5), CPVT2 iPSC-CM (n = 8). In (D, F and G), the effect of ryanodine was expressed as per cent change from control. In (E), the effect of ryanodine was expressed as the change in the fluorescence ratio ΔF_340/380, *P < 0.05, **P < 0.001. Asterisks above columns represent statistically significant effect of ryanodine; asterisk above bars connecting columns represent significant difference between groups. (H) A schematic model explaining the effects of ryanodine in the three groups. Whereas in control cardiomyocytes ryanodine acts as an antagonist and blocks SR Ca²⁺ release, in the mutated cardiomyocytes, due to altered sensitivity of the deregulated RyR2, ryanodine at 10 μM acts as an agonist, and releases SR Ca²⁺ into the cytoplasm.