H2O2 increases and then decreases the occurrence of SOICR. HEK293 cells stably expressing RyR2 were loaded with Fluo-4 in KRH buffer. Cells were superfused with KRH containing 0, 1, or 2 mM Ca2+, with or without various concentrations of H2O2. At the end of each experiment cells were perfused with 20 mM caffeine. Representative traces from cells treated without (A) or with 1 mM H2O2 (B). (C) The frequency of SOICR events, per 5 min bin, normalized to the frequency of events before the application of H2O2. (D) Separate frequency analysis of cells where SOICR was maintained or inhibited in cells exposed to 1 mM H2O2. Control n = 158, 10 μM n = 71, 250 μM n = 93, 1000 μM n = 162. Data shown are mean ± SE. $$ 10 μM p < 0.01; ∗∗∗∗ 250 μM, p < 0.0001; ##### 1000 μM, p < 0.0001; all compared to control (no H2O2).