Large-conductance, voltage- and Ca²⁺-activated K⁺ channels, also known as the BK channels, are widely expressed channels that couple changes in submembrane Ca²⁺ concentration to the regulation of electrical excitability¹. BK channels are formed from four α-subunits arising from the Slowpoke (Slo) gene product². In addition, in smooth muscle and cochlea, an accessory β-subunit can regulate BK channel gating profoundly. At present, four β subunits have been cloned in mammals. β subunits alter the Ca²⁺ sensitivity and gating kinetics of BK channels, greatly contributing to BK channel diversity. On the other hand, they modify the BK channel pharmacological properties, changing toxin binding and acting as receptors for drugs³.

Regulatory β subunits share a putative membrane topology, with two transmembrane segments connected by a 120- residue extracellular loop and with NH₂ and COOH terminals oriented toward the cytoplasm⁴. Each β subunit has a tissue-specific expression and modulates channel function uniquely which provides a major mechanism for diverse BK channel phenotypes in various tissues.

β3 is highly expressed in kidney, heart, and brain⁵. The β3 gene (KCNMB3) associates with Slo1 α subunits and regulate BK channel function. In humans, the β3 gene contains four N-terminal alternative exons that produce four functionally distinct β3 subunits, β3a-d. Three variants, β3a-c, exhibit kinetically distinct inactivation behaviors⁶. A mutation in the β3 gene is linked to idiopathic epilepsy⁷.