Figure 8.

The effect of caffeine on the intracellular Ca²⁺ cycling of control, CPVT1 and CPVT2 iPSC-CM. (A–C) [Ca²⁺]_i transients from control (clone KTN3 day 68), CPVT1 (clone 15.1 day 53) and CPVT2 (clone 20S3 day 60) iPSC-CM, respectively, demonstrating the effect of caffeine. (D) The per cent change in caffeine-induced Ca²⁺ signal amplitude, compared to the pre-caffeine [Ca²⁺]_i transient amplitude. (E) The per cent change in area of the caffeine-induced Ca²⁺ signal, compared to the pre-caffeine [Ca²⁺]_i transient area. Control iPSC-CM (n = 7), CPVT1 iPSC-CM (n = 8), CPVT2 iPSC-CM (n = 8), *P < 0.05, **P < 0.001. Asterisks above columns represent statistically significant effect of caffeine, asterisk above bars connecting columns represent significant difference between groups. (F) A schematic model describing the effects of caffeine in the three groups. In control caffeine depletes SR free Ca²⁺ stores. Because in CPVT2 there is more (due to the mutated CASQ2) luminal free Ca²⁺ than in CPVT1 (due to ‘leaky’ RyR2), the response to caffeine is much more pronounced in CPVT2 than in control and CPVT1 iPSC-CM.