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Research ArticleArticle

Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors

Azahel Rangel, Sergio Sánchez-Armass and Ulises Meza
Molecular Pharmacology February 2010, 77 (2) 202-210; DOI: https://doi.org/10.1124/mol.109.058727
Azahel Rangel
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Sergio Sánchez-Armass
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Ulises Meza
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This article has a correction. Please see:

  • Correction to “Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors” - March 01, 2010

Abstract

The voltage-activated T-type calcium channel (CaV3.2) and the G protein-coupled neurokinin 1 (NK1) receptor are expressed in peripheral tissues and in central neurons, in which they participate in diverse physiological processes, including neurogenic inflammation and nociception. In the present report, we demonstrate that recombinant CaV3.2 channels are reversibly inhibited by NK1 receptors when both proteins are transiently coexpressed in human embryonic kidney 293 cells. We found that the voltage-dependent macroscopic properties of CaV3.2 currents were unaffected during NK1 receptor-mediated inhibition. However, inhibition was attenuated in cells coexpressing either the dominant-negative Gαq Q209L/D277N or the regulator of G protein signaling (RGS) proteins 2 (RGS2) and 3T (RGS3T), which are effective antagonists of Gαq/11. By contrast, inhibition was unaffected in cells coexpressing human rod transducin (Gαt), which buffers Gβγ. Channel inhibition was blocked by 1-[6-[[17β-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) and bisindolylmaleimide I, selective inhibitors of phospholipase Cβ and protein kinase C (PKC), respectively. Inhibition was occluded by application of the PKC activator phorbol-12-myristate-13-acetate. Altogether, these data indicate that NK1 receptors inhibit CaV3.2 channels through a voltage-independent signaling pathway that involves Gαq/11, phospholipase Cβ, and PKC. Our results provide novel evidence regarding the mechanisms underlying T-type calcium channel modulation by G protein-coupled receptors. Functional coupling between CaV3.2 channels and NK1 receptors may be relevant in neurogenic inflammation, neuronal rhythmogenesis, nociception, and other physiological processes.

Footnotes

  • This work was supported by the Consejo Nacional de Ciencia y Tecnología-México [Grant 61248]; and the Universidad Autónoma de San Luis Potosí [Grants C08-FRC-02-53.53, C09-FRC-07-28.28].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.109.058727.

  • ABBREVIATIONS:

    NK1
    neurokinin 1
    PKC
    protein kinase C
    NKA
    neurokinin A
    HEK
    human embryonic kidney
    EGFP
    enhanced green fluorescent protein
    GPCR
    G-protein coupled receptor
    Gαt
    rod transducin
    RGS
    regulator of G protein signaling
    Bis
    bisindolylmaleimide
    PLC
    phospholipase C
    PMA
    phorbol-12-myristate-13-acetate
    U73122
    1-[6-[[17β-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione
    SP
    substance P
    DRG
    dorsal root ganglion.

  • Received June 22, 2009.
  • Accepted October 5, 2009.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 77 (2)
Molecular Pharmacology
Vol. 77, Issue 2
1 Feb 2010
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Research ArticleArticle

Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors

Azahel Rangel, Sergio Sánchez-Armass and Ulises Meza
Molecular Pharmacology February 1, 2010, 77 (2) 202-210; DOI: https://doi.org/10.1124/mol.109.058727

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Research ArticleArticle

Protein Kinase C-Mediated Inhibition of Recombinant T-Type CaV3.2 Channels by Neurokinin 1 Receptors

Azahel Rangel, Sergio Sánchez-Armass and Ulises Meza
Molecular Pharmacology February 1, 2010, 77 (2) 202-210; DOI: https://doi.org/10.1124/mol.109.058727
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