Possible CICR termination mechanisms. (A) SR Ca²⁺ depletion. A reduction in SR Ca²⁺ levels will reduce release flux regardless of RyR gating (as described by their open probability, P_O). However, fateful termination by this mechanism alone is problematic, because the jSR lumen is continually refilled from the rest of the SR. (B) SR luminal control of RyR gating may be modulated either by a direct effect on the RyR itself (red) and/or via an accessory protein such as CSQ (green). However, the extent to which these mechanisms could reduce RyR P_O sufficiently to terminate release is unclear. (C) Stochastic attrition. If all RyRs close simultaneously, then the release flux is terminated. However, it is unlikely that this will occur within the timescale of a Ca²⁺ spark. Stochastic attrition could be accelerated by coupled gating between RyRs, either by direct contact or by a protein linker (X). (D) Induction decay. After CRU activation, jSR Ca²⁺ levels decline which results in a decreasing release flux. The local cytoplasmic Ca²⁺ level is proportional to the release flux, and this is transduced via the steep Ca²⁺ dependence of the RyR closed time. As the closed time becomes longer, it becomes less and less likely for an RyR to reopen to provide the flux and local Ca²⁺ levels required to continue CICR.