Figure 5.

Short exposure to high [H₂O₂] leads to irreversible inhibition of SOICR. HEK293 cells stably expressing RyR2 were loaded with Fluo-4 in KRH buffer. The cells were then transiently (4.5 min) superfused with KRH containing 0, 1, or 2 mM Ca²⁺ and 1 mM H₂O₂ followed by 10 mM DTT (21.5 min). At the end of each experiment cells were perfused with 20 mM caffeine. Representative traces from cells where SOICR (A) was maintained or (B) was inhibited. (C) The frequency of SOICR events, per 5 min bin, normalized to the frequency of events before the application of H₂O₂. Cells treated with H₂O₂ and DTT are displayed as those where SOICR events were maintained or where SOICR ceased by the end of the experiment (Loss of SOICR). Control n = 158, Loss of SOICR n = 188, Maintained SOICR n = 75. Data shown are mean ± SE. ^∗∗∗∗ Loss of SOICR, p < 0.0001; ### and #### Maintained SOICR, p < 0.001 and <0.0001, respectively, compared to control (no H₂O₂).