To determine the number of BK channel puncta that could be activated by an RYR punctum, we performed the following analysis. First, we derived the spatial-temporal [Ca2+] profile resulting from a mean measured ICa(spark) (Fig. 1; Bao et al., 2008). We used the [Ca2+] profile at the peak of ICa(spark) (i.e., 9 ms, which represents the highest [Ca2+] being reached during Ca2+ sparks; see Materials and methods section Simulation of the spatial-temporal profile … and Fig. 7 B in Bao et al., 2008). From this [Ca2+] spatial function, we then calculated the BK Po as a function of the distance (at 0 mV) from the center of the given RYR punctum to the center of its closest neighboring BK channel punctum (see Materials and methods). As shown in Fig. 6 A, at 0 mV, a BK channel localized <300 nm from the center of an RYR punctum would be activated at a Po of 1, and its Po decreases steeply as BK channels localize further away; this Po reaches almost zero when the distance is ∼600 nm. A count of
