Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein ßγ subunits.
Elife
; 62017 08 15.
Article
in En
| MEDLINE
| ID: mdl-28829742
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 ßγ subunits of heterotrimeric G-proteins (Gßγ). Co-expression of Gßγ, but not constitutively active Gαi or Gαo, inhibited TRPM3 currents. TRPM3 co-immunoprecipitated with Gß, and purified Gßγ 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
GTP-Binding Protein beta Subunits
/
GTP-Binding Protein gamma Subunits
/
TRPM Cation Channels
Limits:
Animals
/
Humans
Language:
En
Journal:
Elife
Year:
2017
Document type:
Article
Affiliation country:
United States