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The Journal of Neuroscience, October 1, 2001, 21(19):7587-7597
The C Terminus of the Ca Channel  1B Subunit
Mediates Selective Inhibition by G-Protein-Coupled Receptors
Arthur A.
Simen,
Chong C.
Lee,
Birgitte B.
Simen,
Vytautas P.
Bindokas, and
Richard J.
Miller
Department of Neurobiology, Pharmacology, and Physiology,
University of Chicago, Chicago, Illinois 60637
Inhibition of calcium channels by G-protein-coupled receptors
depends on the nature of the G subunit, although the G  complex is thought to be responsible for channel inhibition. Ca currents in
hypothalamic neurons and N-type calcium channels expressed in HEK-293
cells showed robust inhibition by
Gi/Go-coupled galanin receptors (GalR1),
but not by Gq-coupled galanin receptors (GalR2). However, deletions in
the C terminus of 1B-1 produced Ca channels that were
inhibited after activation of both GalR1 and GalR2. Inhibition of
protein kinase C (PKC) also revealed Ca current modulation by GalR2.
Imaging studies using green fluorescent protein fusions of the C
terminus of 1B demonstrated that activation of the GalR2
receptor caused translocation of the C terminus of 1B-1
to the membrane and co-localization with Gq and PKC. Similar translocation was not seen with a C-terminal truncated splice variant,
1B-2. Immunoprecipitation experiments demonstrated that Gq interacts directly with the C terminus of the 1B
subunit. These results are consistent with a model in which local
activation of PKC by channel-associated Gq blocks modulation of the
channel by G released by Gq-coupled receptors.
Key words:
Ca channels; G-proteins; Gq; C terminus; galanin; G-protein receptors; PKC
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197587-11$05.00/0
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