1. Neuroscience

Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein βγ subunits

  1. Doreen Badheka
  2. Yevgen Yudin
  3. Istvan Borbiro
  4. Cassandra M Hartle
  5. Aysenur Yazici
  6. Tooraj Mirshahi
  7. Tibor Rohacs  Is a corresponding author
  1. New Jersey Medical School, Rutgers, the State University of New Jersey, United States
  2. Weis Center for Research, Geisinger Clinic, United States
https://doi.org/10.7554/eLife.26147
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Cite this article
  1. Doreen Badheka
  2. Yevgen Yudin
  3. Istvan Borbiro
  4. Cassandra M Hartle
  5. Aysenur Yazici
  6. Tooraj Mirshahi
  7. Tibor Rohacs
(2017)
Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein βγ subunits
eLife 6:e26147.
https://doi.org/10.7554/eLife.26147
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Abstract

Transient Receptor Potential Melastatin 3 (TRPM3) channels are activated by heat, and chemical ligands such as pregnenolone sulphate (PregS) and CIM0216. Here we show that activation of receptors coupled to heterotrimeric Gi/o proteins inhibits TRPM3 channels. This inhibition was alleviated by co-expression of proteins that bind the βγ subunits of heterotrimeric G-proteins (Gβγ). Co-expression of Gβγ, but not constitutively active Gαi or Gαo, inhibited TRPM3 currents. TRPM3 co-immunoprecipitated with Gβ, and purified Gβγ proteins applied to excised inside-out patches inhibited TRPM3 currents, indicating a direct effect. Baclofen and somatostatin, agonists of Gi-coupled receptors, inhibited Ca2+ signals induced by PregS and CIM0216 in mouse dorsal root ganglion (DRG) neurons. The GABAB receptor agonist baclofen also inhibited inward currents induced by CIM0216 in DRG neurons, and nocifensive responses elicited by this TRPM3 agonist in mice. Our data uncover a novel signaling mechanism regulating TRPM3 channels.

Article and author information

Author details

  1. Doreen Badheka

    New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Yevgen Yudin

    New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Istvan Borbiro

    New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Cassandra M Hartle

    Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Aysenur Yazici

    New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Tooraj Mirshahi

    Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Clinic, Danville, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Tibor Rohacs

    New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, United States
    For correspondence
    rohacsti@njms.rutgers.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3580-2575

Funding

National Institute of Neurological Disorders and Stroke (R01 NS055159)

  • Tibor Rohacs

National Institute of General Medical Sciences (R01 GM093290)

  • Tibor Rohacs

National Institute of General Medical Sciences (R01GM111913)

  • Tooraj Mirshahi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at Rutgers New Jersey Medical School. Animals were handled according to the approved protocols #14056 (mice) and #14027 (frogs).

Reviewing Editor

  1. Kenton J Swartz, National Institutes of Health, United States

Version history

  1. Received: February 20, 2017
  2. Accepted: June 28, 2017
  3. Accepted Manuscript published: August 15, 2017 (version 1)
  4. Accepted Manuscript updated: August 16, 2017 (version 2)
  5. Version of Record published: September 11, 2017 (version 3)

Copyright

© 2017, Rohacs et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Doreen Badheka
  2. Yevgen Yudin
  3. Istvan Borbiro
  4. Cassandra M Hartle
  5. Aysenur Yazici
  6. Tooraj Mirshahi
  7. Tibor Rohacs
(2017)
Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein βγ subunits
eLife 6:e26147.
https://doi.org/10.7554/eLife.26147

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