Comparison between generic curves used to fit empirical data for P _A0 dependence on [Ca ²⁺ ] _c in isolated RyR1 with curves constructed based on a model that incorporates observations on functional and structural features of RyR1s. The generic curves P_A0 versus [Ca²⁺]_c produced by Eq. A7 used to fit experimental data on isolated RyR1s incorporated in lipid bilayers for [Ca²⁺]_L = 0.01 and 1 mM (Laver et al., 2004) are characterized by three parameters P_i, P_Max, and K_a, which represents [Ca²⁺]_c at half-activation [(P_i+ P_Max)/2]. These curves are compared with equivalent P_A0 versus [Ca²⁺]_c curves generated by Eq. 8, which was derived based on a model where the control hub of one RyR1 molecule becomes activated when all four A-sites of the RyR1 molecule are independently activated. Experimental data can be equally well fit by generic and model-derived curves when the curves are forced to have the same minima, maxima, and intersect at their half-activation point. The ^1pK_CaA values derived from Eq. 9 to ensure that the model-generated curve intersects the generic curve at the mid point were 62.2 and 72.7 nM for [Ca²⁺]_L = 0.01 and 1 mM, respectively, in line with the ^1pK_CaA value of 70 nM in Table 1.