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First published on April 11, 2006; DOI: 10.1124/mol.105.021394

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Received for publication December 1, 2005.
Revised April 7, 2006.
Accepted for publication April 11, 2006.

Phosducin and phosducin like-protein attenuate G-protein coupled receptor mediated inhibition of voltage-gated calcium channels in rat sympathetic neurons

John G Partridge 1, Henry L Puhl III 1, Stephen R Ikeda 1*

1 NIH/NIAAA

* Address correspondence to: E-mail: sikeda{at}mail.nih.gov

Abstract

Phosducin (PDC) has been shown in structural and biochemical experiments to bind the G{beta}{gamma} subunit of heterotrimeric G-proteins. A proposed function of PDC and phosducin like-protein (PDCL) is the sequestration of "free" G{beta}{gamma} from the plasma membrane thereby terminating signaling by G{beta}{gamma}. The functional impact of heterologously expressed PDC and PDCL on N-type calcium channel (CaV2.2) modulation was examined in sympathetic neurons, isolated from rat superior cervical ganglia, using whole-cell voltage-clamp. Expression of PDC and PDCL attenuated voltage-dependent inhibition of N-type calcium channels, a G{beta}{gamma}-dependent process, in a time-dependent fashion. Calcium current inhibition following acute exposure to norepinephrine was minimally altered by PDC or PDCL expression. However, in the continued presence of norepinephrine, PDC or PDCL relieved calcium channel inhibition when compared with control neurons. We observed similar results following activation of heterologously expressed metabotropic glutamate receptors with 100 µM L-glutamate. Neurons expressing PDC or PDCL maintained suppression of inhibition following re-exposure to agonist. Unlike other G{beta}{gamma} sequestering proteins that abolish the acute inhibition of Ca2+ channels, PDC and PDCL require prolonged agonist exposure before effects on modulation are realized.


Key words: Adrenergic, Metabotropic glutamate, Calcium (Votage-Gated Channels), Gi family, G protein regulation


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C. M. Krispel, M. Sokolov, Y.-M. Chen, H. Song, R. Herrmann, V. Y. Arshavsky, and M. E. Burns
Phosducin Regulates the Expression of Transducin {beta}{gamma} Subunits in Rod Photoreceptors and Does Not Contribute to Phototransduction Adaptation
J. Gen. Physiol., August 27, 2007; 130(3): 303 - 312.
[Abstract] [Full Text] [PDF]


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