The concentration dependence of activation of the RYR2 channel by ATP analyzed by the allosteric gating model. (A) Values of PO for 0.005, 1, 8, 15, 26, and 53 mM [Ca2+]L (black squares; open circles; black, gray, and open triangles; and black diamonds, respectively) are displayed as a function of ATP concentration. Solid lines are the best fits by Eq. 3. (B) Values of Po for [Ca2+]C of 100, 180, 250, 330, and 410 nM (open circles; black, gray, and open triangles; and black diamonds, respectively) are displayed as a function of ATP concentration. Solid lines are the best fits by Eq. 3. (C) The relationship between KO0 and fATP at different [Ca2+]L (solid symbols) and [Ca2+]C (open symbols). Solid lines are the apparent linear fits of the data for variable [Ca2+]L in the two ranges of 0.005–8 mM (R = 0.99 and P = 0.066) and 8–53 mM (R = −0.62 and P = 0.37). Dashed line is the apparent linear fit of the data for variable [Ca2+]C (R = 0.97 and P < 0.01). Note that the point representing 1 mM [Ca2+]L and 100 nM [Ca2+]C (partially filled circle) was included in both fits. (D) The relationship between tO0 and fATP at different [Ca2+]L (closed symbols) and [Ca2+]C (open symbols). Solid lines are the apparent linear fits of the data, with R = 0.99 (P < 0.005) for variable [Ca2+]L and R = 0.50 (P > 0.35) for variable [Ca2+]C. Note that the point representing 1 mM [Ca2+]L and 100 nM [Ca2+]C (partially filled circle) was included in both fits. In C and D, labels next to the points specify the conditions of the experiments (L0.005, L1, L15, and L53 for [Ca2+]L of 0.005, 1, 15, and 53 mM, respectively, and C100, C250, and C410 for [Ca2+]C of 100, 250, and 410 nM, respectively).