Assembly of a Ca 2+ ‐dependent BK channel signaling complex by binding to β2 adrenergic receptor

Large‐conductance voltage and Ca 2+ ‐activated potassium channels (BKCa) play a critical role in modulating contractile tone of smooth muscle, and neuronal processes. In most mammalian tissues, activation of β‐adrenergic receptors and protein kinase A (PKA c ) increases BKCa channel activity, contributing to sympathetic nervous system/hormonal regulation of membrane excitability. Here we report the requirement of an association of the β2‐adrenergic receptor (β2AR) with the pore forming α subunit of BKCa and an A‐kinase‐anchoring protein (AKAP79/150) for β2 agonist regulation. β2AR can simultaneously interact with both BKCa and L‐type Ca 2+ channels (Ca v 1.2) in vivo , which enables the assembly of a unique, highly localized signal transduction complex to mediate Ca 2+ ‐ and phosphorylation‐dependent modulation of BKCa current. Our findings reveal a novel function for G protein‐coupled receptors as a scaffold to couple two families of ion channels into a physical and functional signaling complex to modulate β‐adrenergic regulation of membrane excitability.