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EMBO J. 2004 Jun 2;23(11):2196-205. Epub 2004 May 13.

Assembly of a Ca2+-dependent BK channel signaling complex by binding to beta2 adrenergic receptor.

Author information

1
Division of Cardiology and Center for Molecular Cardiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

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 beta-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 beta2-adrenergic receptor (beta2AR) with the pore forming alpha subunit of BKCa and an A-kinase-anchoring protein (AKAP79/150) for beta2 agonist regulation. beta2AR 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 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.

PMID:
15141163
PMCID:
PMC419908
DOI:
10.1038/sj.emboj.7600228
[Indexed for MEDLINE]
Free PMC Article

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