FIGURE 3.

Effects of isoproterenol on systolic Ca²⁺ transients in control and R176Q‐proband‐derived induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CMs) under baseline conditions. A, Confocal line‐scan images (top) and Ca²⁺ transients (bottom) in iPSC‐CMs from the proband with the R176Q variant and healthy control in the presence of 100‐nmol/L isoproterenol (ISO). Red arrows indicate spontaneous SR Ca²⁺ release events that developed during the diastolic phase in PSC‐CMs from the proband. Bar graph summarizing non‐evoked B, Ca²⁺ transient amplitude and C, 10 mmol/L caffeine‐induced SR Load under baseline conditions of control (black) and R176Q (red) iPSC‐CMs. D, Confocal line‐scan images (upper panel) and transients (bottom panel) showing intracellular Ca²⁺ handling loaded with fluro‐4‐AM of evoked (1‐Hz field stimulation) control vs R176Q iPSC‐CMs in the presence of 100‐nmol/L isoproterenol (ISO). SR Ca²⁺ oscillations were further exacerbated in stimulated R176Q iPSC‐CMs. Bar graph summarizing evoked E, Ca²⁺ transient amplitude and F, 10 mmol/L caffeine‐induced SR Ca²⁺ load in the presence of 100‐nmol/L ISO. Open circles represent individual cells. Data presented as mean ± SEM (*P < .05; NS = not statistically significant)