Figure 10

(A) Nearest neighbor allosteric interaction energies, as a function of the states of the interacting channels, for the model using Scheme 2 (from Fig. ​Fig.4,4, shown at top left) augmented by allosteric interactions. (B) SR release currents produced by depolarizations to different voltages, showing a pattern similar to those produced by the phenomenological Schemes 5 and 6 (see Fig. ​Fig.4),4), with termination of release upon repolarization. (C) “Spontaneous” release triggered by exposure to a constant global calcium level for Scheme 2 with and without the allosteric interactions. The interactions cause the activation of the diad to depend cooperatively on calcium, even though each RyR has only a single Ca²⁺ binding site. This suppresses release at physiologic levels of global [Ca²⁺], conferring global stability on the model.