Semilogarithmic plot of ^nc P _I0 and ^c P _I0 dependence on the combined concentrations of Ca ²⁺ and Mg ²⁺ in the junctional space ([CaMg] _js ). The inhibition terms ^ncP_I0 and ^cP_I0 express the probabilities that ^ncRyR1s and, respectively, ^cRyR1s are not inhibited at the low affinity Ca²⁺/Mg²⁺ I1 sites. Under resting conditions, when the DHPRs are not activated, both terms display 50% inhibition at 50 µM [CaMg]_js but the increased DHPR-dependent level of cooperativity between the four I1 sites of ^cRyR1s translates to greater inhibition at [CaMg]_js > 50 µM in ^cRyR1s than ^ncRyR1s. A 30-fold rise of ^4pK_in induced by DHPR activation would shift the ^cP_I0 curve to the right, triggering rapid Ca²⁺ release from SR (see Fig. 1 and text).