Suppression of KCNQ/M Potassium Channel in Dorsal Root Ganglia Neurons Contributes to the Development of Osteoarthritic Pain
- PMID: 30759446
- DOI: 10.1159/000496422
Suppression of KCNQ/M Potassium Channel in Dorsal Root Ganglia Neurons Contributes to the Development of Osteoarthritic Pain
Abstract
Osteoarthritic pain has a strong impact on patients' quality of life. Understanding the pathogenic mechanisms underlying osteoarthritic pain will likely lead to the development of more effective treatments. In the present study of osteoarthritic model rats, we observed a reduction of M-current density and a remarkable decrease in the levels of KCNQ2 and KCNQ3 proteins and mRNAs in dorsal root ganglia (DRG) neurons, which were associated with hyperalgesic behaviors. The activation of KCNQ/M channels with flupirtine significantly increased the mechanical threshold and prolonged the withdrawal latency of osteoarthritic model rats at 3-14 days after model induction, and all effects of flupirtine were blocked by KCNQ/M-channel antagonist, XE-991. Together, these results indicate that suppression of KCNQ/M channels in primary DRG neurons plays a crucial role in the development of osteoarthritic pain.
Keywords: Dorsal root ganglia; KCNQ/M channels; Modulators; Osteoarthritic pain.
© 2019 S. Karger AG, Basel.
Similar articles
-
Suppression of KCNQ/M (Kv7) potassium channels in dorsal root ganglion neurons contributes to the development of bone cancer pain in a rat model.Pain. 2013 Mar;154(3):434-448. doi: 10.1016/j.pain.2012.12.005. Epub 2012 Dec 20. Pain. 2013. PMID: 23352759
-
KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons.J Physiol. 2006 Aug 15;575(Pt 1):175-89. doi: 10.1113/jphysiol.2006.113308. Epub 2006 Jun 15. J Physiol. 2006. PMID: 16777937 Free PMC article.
-
Antinociceptive Efficacy of Retigabine and Flupirtine for Gout Arthritis Pain.Pharmacology. 2020;105(7-8):471-476. doi: 10.1159/000505934. Epub 2020 Feb 14. Pharmacology. 2020. PMID: 32062659
-
Involvement of HDAC2-mediated kcnq2/kcnq3 genes transcription repression activated by EREG/EGFR-ERK-Runx1 signaling in bone cancer pain.Cell Commun Signal. 2024 Aug 27;22(1):416. doi: 10.1186/s12964-024-01797-2. Cell Commun Signal. 2024. PMID: 39192337 Free PMC article.
-
The therapeutic potential of neuronal K V 7 (KCNQ) channel modulators: an update.Expert Opin Ther Targets. 2008 May;12(5):565-81. doi: 10.1517/14728222.12.5.565. Expert Opin Ther Targets. 2008. PMID: 18410240 Review.
Cited by
-
Molecular basis for ligand activation of the human KCNQ2 channel.Cell Res. 2021 Jan;31(1):52-61. doi: 10.1038/s41422-020-00410-8. Epub 2020 Sep 3. Cell Res. 2021. PMID: 32884139 Free PMC article.
-
Ion channels in osteoarthritis: emerging roles and potential targets.Nat Rev Rheumatol. 2024 Sep;20(9):545-564. doi: 10.1038/s41584-024-01146-0. Epub 2024 Aug 9. Nat Rev Rheumatol. 2024. PMID: 39122910 Review.
-
Effective Activation of BKCa Channels by QO-40 (5-(Chloromethyl)-3-(Naphthalen-1-yl)-2-(Trifluoromethyl)Pyrazolo [1,5-a]pyrimidin-7(4H)-one), Known to Be an Opener of KCNQ2/Q3 Channels.Pharmaceuticals (Basel). 2021 Apr 21;14(5):388. doi: 10.3390/ph14050388. Pharmaceuticals (Basel). 2021. PMID: 33919092 Free PMC article.
-
Evidence for Dual Activation of IK(M) and IK(Ca) Caused by QO-58 (5-(2,6-Dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-pyrazolol[1,5-a]pyrimidin-7-one).Int J Mol Sci. 2022 Jun 24;23(13):7042. doi: 10.3390/ijms23137042. Int J Mol Sci. 2022. PMID: 35806047 Free PMC article.
-
The M-current works in tandem with the persistent sodium current to set the speed of locomotion.PLoS Biol. 2020 Nov 13;18(11):e3000738. doi: 10.1371/journal.pbio.3000738. eCollection 2020 Nov. PLoS Biol. 2020. PMID: 33186352 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
