Consistent with the findings in a variety of smooth muscles (Du et al., 2005; Yang et al., 2005; Essin and Gollasch, 2009; Yang et al., 2009; Clark et al., 2010), we detected all three types of RYRs at mRNA and protein levels in mouse ASM. As a result, an intriguing question arises as to the types of RYRs that functionally couple with BK channels. Our immunostaining results show that both RYR1 and RYR2 localize close to the plasma membrane and thus are well positioned to be responsible for the generation of STOCs. Interestingly, RYR3s concentrate in the perinuclear region, and Ca2+ release by an individual RYR3 cluster is therefore unable to activate BK channels in the plasma membrane. Therefore, we can conclude that RYR3 does not couple with BK channels to generate STOCs.
