FIGURE 8.

BK_Ca-Cav1.2 complex in VSMCs. A, BK_Ca-Cav1.2 complex can consist of one BK_Ca (a tetrameric BKα assembly) and four Cav1.2 channels. In caveolin-1-deficient (KO) myocytes, the interaction between BK_Ca and Cav1.2 is attenuated by following reasons. The BK_Ca-Cav1.2 complex, which is facilitated by the accumulation of these channels in caveolae by the interaction with caveolin-1, is reduced in KO myocytes. The number of Cav1.2 within the BK_Ca-Cav1.2 complex is also reduced in KO myocytes. B, BK_Ca can be activated by three steps of Ca²⁺ increase. The first is Ca²⁺ influx from tightly coupled Cav1.2. The second is Ca²⁺ release from loosely coupled RyR, i.e. CICR. The third step is global Ca²⁺ level elevation evoked by the Ca²⁺ wave. We propose that large portions of the BK_Ca-Cav1.2 complexes are localized in caveolae and that the complex of 1 BK_Ca with 4 Cav1.2 cluster may contribute to initiate Ca²⁺ local events in caveolae as the key membrane structure in Ca²⁺ microdomain, which, however, includes the effective negative feedback mechanism for cytosolic Ca²⁺ regulation.