Fig. 1: The BH4 domains of Bcl-2 and Bcl-X_L inhibit RyR-mediated Ca²⁺ release in PACs.

a Linear representation of the Bcl-2/Bcl-X_L protein together with the sequences used to design the BH4 domain peptides originating from Bcl-2 and Bcl-X_L and the predicted secondary structure using the PSIPRED secondary structure predictor (http://bioinf.cs.ucl.ac.uk/psipred/). b–d Typical traces of the Fluo-4AM single-cell Ca²⁺ measurements performed in mouse PACs. At the start of each experiment cells were perfused with NaHEPES containing DMSO (vehicle). After establishing the baseline (200 s), CCK (5 pM) was added and RyR-mediated Ca²⁺ oscillations were measured for 5 min. Then, 50 µM of either the control peptide (b), the BH4 domain of Bcl-2 (c), or the BH4 domain of Bcl-X_L (d) were added for 10 min, in the continuous presence of 5 pM CCK. e Quantification of the experiments: The area under the curve per second (AUC/sec) of the CCK-induced Ca²⁺ release after peptide addition (10 min recording) was compared to the AUC/sec before peptide addition (5 min recording). Each data point represents the measurement of an individual cell. The average values ± SEM are shown (P-value <0.0001). At least three independent experiments were performed per condition (N ≥ 3). For each condition at least 35 cells were recorded