Predicted time course of [Ca ²⁺ (t)] _js and Ca ²⁺ -release properties of mammalian muscle fibers following sudden, DHPR-activation dependent reduction of Mg ²⁺ inhibition at Ca ²⁺ /Mg ²⁺ I1 sites of ^c RyR1s. (A) Time course of [Ca²⁺(t)]_js on 0.5 s and an expanded time scale in the inset, following maximal DHPR activation in a couplon at t = 0. The peak of [Ca²⁺(t)]_js exceeds 70 µM due to the massive increase in the junctional SR permeability for Ca²⁺ and the limited diffusiveness of Ca²⁺ across the JS/cytosol barrier. (B) Time course of Ca²⁺ and Mg²⁺ occupancy of individual/protomeric A-sites of RyR1s in a couplon. (C) Time course of SR Ca²⁺ depletion ([Ca²⁺(t)]_SR), changes in junctional SR permeability for Ca²⁺ (k_SRJS) (inset, lefthand side vertical scale), and open probability of one DHPR-coupled RyR1 (^cP₀(t)) and one DHPR-noncoupled RyR1 (^ncP₀(t)) in the JS (inset, righthand side vertical scale). Before stimulation ^ncP₀(t)/(^cP₀(t)) ≈ 400 and decreases to ≈ 0.0027 at the peak of SR permeability for Ca²⁺. (D) Time course of SR Ca ²⁺—release flux into the cytosol (µM Ca²⁺ released per volume of cytosol per ms). The inset depicts the predicted SR Ca ²-release flux into the cytosol if the SR Ca²⁺ pump was very active, returning 200 μM Ca²⁺ (relative to SR volume) ms⁻¹ (1 – [Ca²⁺(t)]_SR/400 µM), which would fill the empty SR in a non-stimulated “fiber” in <200 ms. Note that the peak SR Ca²⁺ efflux is hardly affected when the SR Ca²⁺ pump is active. The orange lines in B and C show the maximum probability of A-site occupancy (1.0) and [Ca²⁺(0)]_SR, respectively.