Figure 4. H₂O₂‐induced increases in mEPSC frequency are due to intracellular Ca²⁺ release via RyR and IP3R .

A, Dant (10 μm), an RyR antagonist, completely blocked the H₂O₂‐induced increase in mEPSC frequency but not the subsequent depression. B, the IP₃R antagonist 2‐APB (200 μm) completely blocked both the increase and depression in frequency. Note that the increase not only was blocked but was reduced with respect to the control after 5 min of H₂O₂ superfusion (38.9 ± 3.2% of control, n = 6). C, summary of mEPSC frequency during (left) and after (right) H₂O₂ superfusion with TTX alone (n = 11) or with CSA (a MPT blocker/calcineurin inhibitor, 10 μm; n = 6), Dant (10 μm; n = 5–8), or 2‐APB (200 μm; n = 6) relative to the control (mean ± SEM). Values on the left indicate maximal values of mEPSC frequency relative to the control 1.5–6 min after H₂O₂ superfusion. P values were determined by one‐way ANOVA with a Bonferroni post hoc test. D, FFA (100 μm), a TRPM2 channel blocker, did not block the H₂O₂‐induced increase and subsequent depression in mEPSC frequency. E, summary of mEPSC frequency recordings in the presence of FFA (mean ± SEM, n = 7). Values in the charts correspond to percentage change in maximal values of mEPSC frequency relative to the control during H₂O₂ superfusion and after washout. The P value was determined by a paired t test. The holding potential was −70 mV for all recordings. Washout indicates the 10 min period after initiating H₂O₂ washout.