Assembly of a Ca2+-dependent BK channel signaling complex by binding to β2 adrenergic receptor

Guoxia Liu, Jingyi Shi, Lin Yang, Luxiang Cao, Soo Mi Park, Jianmin Cui, Steven O. Marx

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Large-conductance voltage and Ca2+-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 (PKAc) 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 Ca2+ channels (Cav1.2) 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.

Original languageEnglish
Pages (from-to)2196-2205
Number of pages10
JournalEMBO Journal
Volume23
Issue number11
DOIs
StatePublished - Jun 2 2004

Keywords

  • BKCa
  • Kinase
  • Macromolecular complex
  • Phosphorylation
  • β2AR

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