Effect of altering RyR2 opening and closing rates from control (blue lines, parameters given in Table S3 and cytoplasmic [Ca ²⁺ ] dependencies shown in Fig. S3 ). (A–D) Resulting time courses of [Ca²⁺] in the cytoplasm (A) and LSR (B) and the total Ca²⁺ fluxes through all 371 dyads in the x-y plane originating from the initial flux transients from sparks and embers (C) or the subsequent flux plateaus from embers (D). Values were taken near the longitudinal axis (x = 1 μm and y = 1 μm, z = 25 μm [midpoint of the longitudinal axis]). In these simulations, [Fluo-4] = 0.05 mM so that waves would form under all conditions tested. (E and F) Green lines show a threefold reduction in opening and closing rates (fast kinetics with the same open probability), and red lines show a threefold reduction in opening rates at diastolic [Ca²⁺] (diastolic block).