PubMed 15953418

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Cav2.2

Title: G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels.

Authors: Heather L Agler, Jenafer Evans, Lai Hock Tay, Molly J Anderson, Henry M Colecraft, David T Yue

Journal, date & volume: Neuron, 2005 Jun 16 , 46, 891-904

PubMed link:

Voltage-dependent G protein (Gbetagamma) inhibition of N-type (CaV2.2) channels supports presynaptic inhibition and represents a central paradigm of channel modulation. Still controversial are the proposed determinants for such modulation, which reside on the principal alpha1B channel subunit. These include the interdomain I-II loop (I-II), the carboxy tail (CT), and the amino terminus (NT). Here, we probed these determinants and related mechanisms, utilizing compound-state analysis with yeast two-hybrid and mammalian cell FRET assays of binding among channel segments and G proteins. Chimeric channels confirmed the unique importance of NT. Binding assays revealed selective interaction between NT and I-II elements. Coexpressing NT peptide with Gbetagamma induced constitutive channel inhibition, suggesting that the NT domain constitutes a G protein-gated inhibitory module. Such inhibition was limited to NT regions interacting with I-II, and G-protein inhibition was abolished within alpha1B channels lacking these NT regions. Thus, an NT module, acting via interactions with the I-II loop, appears fundamental to such modulation.