Figure 4.

Ca²⁺ Sensitivity of Isogenic Pairs of hiPSC-CM EHTs

iPSC-CM EHT were exposed to increasing concentrations of Ca²⁺ in Tyrode's solution and contractions were recorded while being stimulated at 1 Hz. In (Ai), the force of EHTs was calculated as a percentage of maximum for the unedited lines, with E99K lines shown in red and wild-type in black. EC₅₀ values were calculated using absolute force and are shown for the unedited lines in (Aii). The comparison of normalized forces are shown for the isogenic pairs of E99K1 (Bi), NC (Bii), and E99K2 (Biii); the dotted line is the average with arrhythmogenic EHTs removed. In (Ci) to (Ciii), the corresponding EC₅₀ values for isogenic lines were calculated using absolute force.

All error bars represent SEM. Significance was determined by Student’s t test and one-way ANOVA, ^∗p < 0.05, ⁺⁺p < 0.01, and ⁺⁺⁺p < 0.001. n = 7 E99K1, 2 E99K1-Corr, 7 NC-Edit-E99K, 7 NC, 5 E99K2, and 6 E99K2-Corr. Red, mutant ACTC E99K; black, wild-type.