Localization of RYR1 and RYR2 near the plasma membrane raises the question of whether both channels couple with the same population of BK channels. Two lines of evidence indicate that RYR1s and RYR2s could activate different clusters of BK channels. First, the distance between RYR1s and their closest BK channel cluster is shorter than that between RYR2 and BK channels. Second, the numbers of BK channels that can be activated by RYR1s is more than that by RYR2s. Therefore, our results suggest that RYR1s and RYR2s could constitute independent Ca2+ spark microdomains (Fig. 8 D).
