nucleus, so only RYR1 and RYR2 appear functionally able to couple with BK channels; (b) both RYRs and BK channels form clusters; and (c) for a given RYR1 or RYR2 cluster, two to three BK clusters on average are randomly distributed within the region where the [Ca2+] is high enough to produce STOC-like events. Combining a kinetic model of BK channels, the spatial-temporal Ca2+ profile generated by sparks, and the spatial organization of RYRs and BK channels, we can recapitulate the essential features of STOCs activated by Ca2+ sparks. Therefore, we are able to provide a mechanistic explanation of Ca2+ spark–induced STOC based on the physical relationship of these channels in the same type of cells.
