In spite of the physiological importance and pathological implications of Ca2+ sparks and STOCs in smooth muscle, the spatial organization of BK channels and RYRs is still poorly understood. However, this knowledge is critical to understanding how Ca2+ sparks activate STOCs. Previously, we estimated that in amphibian gastric smooth muscle, BK channels are exposed to 10 µM [Ca2+] during a Ca2+ spark, leading to a suggestion that RYRs and BK channels form a microdomain in which BK channels are at a higher density than other regions of the cells (ZhuGe et al., 1999, 2002). Interestingly, although Pérez et al. (2001) derived that BK channels in cerebral smooth muscle cells are activated by a similar level of [Ca2+] caused by Ca2+ sparks, these authors proposed that BK channels localize homogeneously in the surface membrane and that a Ca2+ spark activates them localized in an area of 13 µm2. This leads to a possibility that there might be a difference between amphibian and mammalian cells with regards to the distribution of BK channels in the Ca2+ spark domains. Such a difference should also motivate an analysis that can directly localize and visualize RYRs and BK channels in smooth muscle cells.