Effect of SERCA inhibition on SR [Ca2+]. (A) Simulated effect of SERCA inhibition by thapsigargin (TG, Ap = 0) on [Ca2+]nsr (black line) and whole-cell Ca2+ spark rate (red circles). (B) Simulated effect of a RyR-specific antagonist, ruthenium red (RuR) on [Ca2+]nsr (black line) and whole-cell Ca2+ spark rate (red circles), before and after SERCA inhibition by TG. In each case, [Ca2+]i was fixed at 150 nM to mimic experimental conditions in permeabilized cells (see Zima et al. (8)). RuR is modeled here by disabling all but 2% of the RyRs in the model cell and giving the functional RyRs the kinetics of nonjunctional, rogue RyRs (vryr = 0, vryr,nj = 1.01 s−1).