Journal
EMBO JOURNAL
Volume 23, Issue 11, Pages 2196-2205Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.emboj.7600228
Keywords
BKCa; beta 2AR; kinase; macromolecular complex; phosphorylation
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Funding
- NHLBI NIH HHS [R01 HL070393] Funding Source: Medline
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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 beta-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 beta2-adrenergic receptor (beta2AR) with the pore forming alpha subunit of BKCa and an A-kinase-anchoring protein (AKAP79/150) for beta2 agonist regulation. b2AR can simultaneously interact with both BKCa and L-type Ca2+ channels (Ca(v)1.2) in vivo, which enables the assembly of a unique, highly localized signal transduction complex to mediate Ca2+- 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 beta-adrenergic regulation of membrane excitability.
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