Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein βγ subunits
- New Jersey Medical School, Rutgers, the State University of New Jersey, United States
- Weis Center for Research, Geisinger Clinic, United States
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
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
- Kenton J Swartz, National Institutes of Health, United States
Publication history
- Received: February 20, 2017
- Accepted: June 28, 2017
- Accepted Manuscript published: August 15, 2017 (version 1)
- Accepted Manuscript updated: August 16, 2017 (version 2)
- 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.
Metrics
-
- 2,386
- Page views
-
- 429
- Downloads
-
- 48
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein βγ subunits
eLife 6:e26147.
https://doi.org/10.7554/eLife.26147
