FIGURE 3.

K_V1 and BK complexes and membrane potential regulation. K⁺ channel activity provides negative-feedback regulation of membrane potential and limits Ca_V1.2 activity leading to VSM relaxation (Nelson, 1992). The scaffolding protein PSD95 facilitates the regulation of K_V1 channels by β1AR/PKA signaling (Moore et al., 2015). BK channels are activated by the release of Ca²⁺ from the SR through RyR (Ca²⁺ sparks) (Jaggar et al., 1998). Ca²⁺ influx through TRPV4 channels activates the RyR/BK channel axis, which hyperpolarizes VSM membrane potential (Earley et al., 2005). Caveolae facilitate spatial proximity between Ca_V3.2 and RyR, Ca_V3.2-mediated Ca²⁺ influx prompts RyR, and the resultant Ca²⁺ sparks activate BK channels (Harraz et al., 2014; Hashad et al., 2018), which hyperpolarizes VSM membrane potential and limits VGCC activity leading to relaxation. Graphics created with BioRender.com.