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Research ArticlePerspective

G Protein-Mediated Inhibition of Cav3.2 T-Type Channels Revisited

Edward Perez-Reyes
Molecular Pharmacology February 2010, 77 (2) 136-138; DOI: https://doi.org/10.1124/mol.109.062133
Edward Perez-Reyes
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Abstract

T-type calcium channels are important modulators of both membrane potential and intracellular Ca2+ concentration, allowing them to play key roles in such diverse processes as aldosterone production from adrenal glomerulosa cells to boosting pain signals in nociceptors. In both these examples, the Cav3.2 isoform mediates Ca2+ influx. This isoform is also of particular interest because mutations in its gene (CACNA1H) that enhance channel activity have been associated with idiopathic generalized epilepsies, whereas mutations that disrupt its activity have been associated with autism spectrum disorders. Block of T-channel activity has been proposed to contribute to the therapeutic usefulness of a wide variety of drugs, such as antihypertensives, antipsychotics, and antidepressants. Recent evidence strongly supports the hypothesis that block of Cav3.2 channels might be useful in the treatment of neuropathic pain. Therefore, it is of particular interest that Cav3.2 channels are exquisitely regulated by G protein-coupled receptors and various downstream effectors. This Perspective summarizes recent findings (p. 202) on this regulation and the novel pathways specifically activated by either neurokinin I, corticotropin-releasing factor receptor 1, or dopamine D1 receptors.

Footnotes

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

    doi:10.1124/mol.109.062133

  • Please see the related article on page 202.

  • ABBREVIATIONS:

    GPCR
    G protein-coupled receptor
    NK1
    neurokinin 1
    HEK
    human embryonic kidney
    PLCβ
    phospholipase C β
    PKC
    protein kinase C
    CRF-1
    corticotropin-releasing factor receptor 1
    U73122
    1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione.

  • Received November 4, 2009.
  • Accepted November 6, 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 ArticlePerspective

G Protein-Mediated Inhibition of Cav3.2 T-Type Channels Revisited

Edward Perez-Reyes
Molecular Pharmacology February 1, 2010, 77 (2) 136-138; DOI: https://doi.org/10.1124/mol.109.062133

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Research ArticlePerspective

G Protein-Mediated Inhibition of Cav3.2 T-Type Channels Revisited

Edward Perez-Reyes
Molecular Pharmacology February 1, 2010, 77 (2) 136-138; DOI: https://doi.org/10.1124/mol.109.062133
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