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Article

  • The EMBO Journal (2004) 23, 2196 - 2205
  • doi:10.1038/sj.emboj.7600228

Published online: 13 May 2004

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

Guoxia Liu1, Jingyi Shi2, Lin Yang1, Luxiang Cao3, Soo Mi Park1, Jianmin Cui2 and Steven O Marx1

  1. Division of Cardiology and Center for Molecular Cardiology, Department of Medicine and Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
  2. Cardiac Bioelectricity Research and Training Center and Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA
  3. Department of Physiology and Cellular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY, USA

Correspondence to:

Steven O Marx, Division of Cardiology and Center for Molecular Cardiology, Department of Medicine and Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Tel.: +1 212 305 0271; Fax: +1 212 342 0475; E-mail: sm460@columbia.edu

Received 7 January 2004; Accepted 14 April 2004

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.

  • Keywords:

    • BKCa,
    • beta2AR,
    • kinase,
    • macromolecular complex,
    • phosphorylation