AI Article Synopsis
- TRPM3 channels, which respond to heat and certain chemicals, can be inhibited by receptors that are linked to Gi/o proteins.
- Co-expressing specific proteins that bind to Gβγ subunits counteracts this inhibition of TRPM3 channels.
- The research reveals a new signaling pathway that influences TRPM3 channel activity, impacting calcium signals and nociceptive responses in neurons.
Article 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 Ca signals induced by PregS and CIM0216 in mouse dorsal root ganglion (DRG) neurons. The GABA 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593506 | PMC |
| http://dx.doi.org/10.7554/eLife.26147 | DOI Listing |
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