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Assembly of a Ca 2+ ‐dependent BK channel signaling complex by binding to β2 adrenergic receptor
Author(s) -
Liu Guoxia,
Shi Jingyi,
Yang Lin,
Cao Luxiang,
Park Soo Mi,
Cui Jianmin,
Marx Steven O
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600228
Subject(s) - biology , adrenergic receptor , receptor , signal transduction , microbiology and biotechnology , genetics , biophysics
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.