G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons

Talisia Quallo; Omar Alkhatib; Clive Gentry; David A Andersson; Stuart Bevan

doi:10.7554/eLife.26138

G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons

Talisia Quallo, Omar Alkhatib, Clive Gentry, David A Andersson, Stuart Bevan

Wolfson SPaRC

King's College London

Research output: Contribution to journal › Article › peer-review

79 Citations (Scopus)

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Abstract

Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by phosphoinositide PI(4,5)P2 hydrolysis and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM3 expressed in mouse dorsal root ganglion (DRG) neurons is inhibited by agonists of the Gi-coupled µ opioid, GABA-B and NPY receptors. These agonist effects are mediated by direct inhibition of TRPM3 by Gβγ subunits, rather than by a canonical cAMP mediated mechanism. The activity of TRPM3 in DRG neurons is also negatively modulated by tonic, constitutive GPCR activity as TRPM3 responses can be potentiated by GPCR inverse agonists. GPCR regulation of TRPM3 is also seen in vivo where Gi/o GPCRs agonists inhibited and inverse agonists potentiated TRPM3 mediated nociceptive behavioural responses.

Original language	English
Article number	e26138
Number of pages	22
Journal	eLife
Volume	6
Early online date	15 Aug 2017
DOIs	https://doi.org/10.7554/eLife.26138
Publication status	Published - 15 Aug 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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G protein βγ subunits_Publishedonline15August2017_GOLD VoR (CC BY)Final published version, 4.8 MBLicence: CC BY

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AU - Quallo, Talisia

AU - Alkhatib, Omar

AU - Gentry, Clive

AU - Andersson, David A

AU - Bevan, Stuart

PY - 2017/8/15

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G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons

Abstract

Keywords

UN SDGs

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