Systolic and diastolic SCaEs in perfused R4496C+/− RyR2 mouse ventricles. A, Cai optical tracings at baseline (sinus rhythm) in wild-type littermate control and R4496C+/− knock-in mice. Note diastolic SCaEs (red arrowheads) only in the R4496C+/− mouse ventricle. B, Simultaneous Cai and Vm tracings during ventricular pacing at various pacing cycle lengths (PCL) after creating AV block in the R4496C+/− mouse ventricle with diastolic SCaEs at baseline. As the cycle length was prolonged, systolic SCaEs (red arrows) became larger and TAs (asterisks) developed during escape rhythm at a cycle length of 623 ms. C, Effect of VK-II-36 (10 μM) on systolic and diastolic SCaEs. (Left panels) Representative Cai tracings before and after VK-II-36 in the R4496C+/− mouse ventricle. (Right panel) Mean ± SEM values of the amplitudes of diastolic and systolic SCaEs at a PCL of 500 ms before and after the addition of VK-II-36 (n = 4, both P < 0.05).