FIGURE 5.

Sarcoplasmic reticulum (SR)‐mitochondria Ca²⁺ transfer upon heterologous expression of zVDAC2 and zVDAC2^AAA in HL‐1 cardiomyocytes. (a) Representative recordings of mitochondrial Ca²⁺ upon application of 10‐mM caffeine to induce SR calcium release from permeabilized HL‐1 cardiomyocytes. Traces from control conditions (black), recordings in the presence of 10‐μM ruthenium red to block mitochondrial Ca²⁺ uptake (RuR, grey) and in the presence of 10‐μM efsevin (red) are shown for native HL‐1 cells (native), cells transduced with shRNA targeting the endogenous mouse mVDAC2 (shmVDAC2), and cells overexpressing zVDAC2 and zVDAC2^AAA, respectively. (b) Statistical analysis of SR‐mitochondria Ca²⁺ transfer experiments. While native HL‐1 cardiomyocytes showed an efsevin‐sensitive uptake of Ca²⁺ into mitochondria (n = 21 for control, n = 7 for RuR, and n = 18 for efsevin), this uptake was abolished upon knock‐down of the endogenous mVDAC2 (shmVDAC2, n = 24 for control, n = 8 for RuR, n = 15 for efsevin). Subsequent heterologous expression of zVDAC2 (shmVDAC2, n = 21 for control, n = 7 for RuR, n = 15 for efsevin) and zVDAC2^AAA (shmVDAC2^AAA, n = 18 for control, n = 6 for RuR, n = 18 for efsevin) revealed restoration of SR‐mitochondria Ca²⁺ transfer. However, only zVDAC2 but not zVDAC2^AAA was sensitive to efsevin (Kruskal–Wallis test with Dunn's post hoc test)