Figure 11.

(A) Global cytosolic [Ca²⁺] for the model using Scheme 2 (see Fig. 4) with and without allosteric interactions is shown. With Na/Ca release disabled, there is no relaxation of global [Ca²⁺] after a stimulus; normal relaxation is produced when allosteric interactions between RyRs are included. (B) Global instability of the model using Scheme 2 is revealed by major calcium release when the diads are exposed to resting global background [Ca²⁺] (100 nM) in the absence of depolarization. Inclusion of allosteric interactions eliminates this background sensitivity by requiring cooperative activation by Ca²⁺ bound to different RyRs. (C) The effect of the allosteric interactions is basically inhibitory. As a result, if the number of RyRs per diad is reduced by leaving vacancies in the RyR lattice, there is a paradoxical increase in the rate of SR calcium release, until the number of RyR remaining is no longer sufficient to support the release. (D) The allosteric suppression of spontaneous release triggered by background calcium (C) is very sensitive to completeness of the RyR lattice. Introduction of small numbers of vacancies per diad unmasks the unstable release characteristic of Scheme 2 RyR activation by a single bound Ca²⁺. The effect of reducing the number of RyRs by introducing vacancies in the lattice is much larger than the effect of simply reducing the size of a complete array, which has only a slight effect on global stability.