Cytosolic Ca²⁺ regulates the effect of luminal Ca²⁺ on the RYR2 channel. (A) The [Ca²⁺]_L dependence of $POmax$ in the presence of 180 and 410 nM [Ca²⁺]_C (open and black circles, respectively). Solid lines are Hill equation fits obtained by fitting the whole dataset at 180 and 410 nM [Ca²⁺]_C simultaneously when n_H as a fitted parameter was shared, whereas EC₅₀ was free. The dotted line represents the data obtained for 100 nM [Ca²⁺]_C that are replotted from Fig. 2 B (middle). (B) The cytosolic Ca²⁺ dependence of EC₅₀ for luminal Ca²⁺. Data are presented as average ± SEM. (C) The values of t_O0 determined in the absence of ATP on 30 s intervals for 100 nM and 410 nM [Ca²⁺]_C (open and black circles, respectively) are displayed as a function of [Ca²⁺]_L. (D) The values of t_O determined in the presence of 10 mM ATP on 30-s intervals for 100 and 410 nM [Ca²⁺]_C (open and black circles, respectively) are displayed as a function of [Ca²⁺]_L. Error bars in C and D are shown only when the SEM is larger than symbol size.