Figure 2: Structure and physiology of BKCa channels. (a) BKCa channels are composed of two different subunits: the pore-forming α subunit and the auxiliary β subunits. A functional channel is made up by the association of four α and four β1 subunits. Although a single gene codes for α, splicing leads to variants that are different in biophysical properties and/or intracellular localization. (b) In smooth muscles, membrane depolarization and/or intracellular Ca2+ cause the influx of Ca2+ through voltage-dependent Ca2+ channels (VDCCs). This in turn causes a rise in intracellular Ca2+ levels and smooth muscle contraction. Increases in Ca2+ levels facilitate Ca2+ binding to ryanodine receptors (RRs) in the sarcoplasmic reticulum (SR), which produces a localized Ca2+ release (Ca2+ spark) that activates the BKCa channels. Activation of BKCa channels causes efflux of K+, hyperpolarization of the cell membrane, closure of VDCC, prevention of Ca2+ entry, and eventually smooth muscle relaxation. Adapted from Garcia et al. [27].