Pharmacological Relevance of β-, γ-, and LINGO Auxiliary Subunits in BK Channel Modulation

Large-conductance voltage- and Ca²⁺-activated potassium (BK) channels are essential regulators of physiological processes including smooth muscle tone, neurotransmitter release, and neuronal excitability. While the pore-forming α-subunit is sufficient for channel function, the remarkable diversity of BK currents in native tissues arises from its association with three structurally distinct auxiliary subunit families: β, γ, and the recently identified LINGO, each one containing four members. These auxiliary subunits significantly alter channel gating, kinetics, and pharmacological responsiveness. Moreover, their tissue-specific expression patterns, together with the distinct pharmacological sensitivities they confer, provide a promising strategy for the development of subunit-selective modulators capable of minimizing the side effects commonly associated with the widespread systemic distribution of the α-subunit. In this review, we summarize the tissue-specific distribution of auxiliary subunits and provide a systematic update on the pharmacological profile of BK channel modulation as a function of its subunit composition.