In ASM, Ca2+ sparks activate BK channels to generate STOCs and Ca2+-activated Cl− channels to give rise to STICs (ZhuGe et al., 2010). To obtain insight into the relationship between Ca2+ sparks and STOCs, two approaches were used. First, the cells were voltage clamped at the reversal potential for Cl− (ECl, 0 mV) so STICs would not occur. Second, Ca2+ sparks were recorded at 333 Hz so their temporal relationship with STOCs could be determined with more accuracy. With these approaches, we detected a close temporal correlation between Ca2+ sparks and STOCs (Fig. 1 A). The onset of Ca2+ sparks coincided with the onset of a STOC or preceded it by 3 ms on average (range of 0–12 ms, n = 35). The rise time of Ca2+ spark signal mass was 32 ± 2 ms, which was not significantly different from TTODSTOC (time from the onset of the rise to the onset of the decay of STOCs; 29 ± 2 ms; P = 0.148, n = 35; Fig. 1 B, a). Such close temporal correlation suggests that RYRs underlying Ca2+ sparks and BK channels underlying STOCs localize in proximity to each other in these cells.
