Biology:TRPM3
 Generic protein structure example |
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.[1]
Function
The product of this gene belongs to the family of transient receptor potential (TRP) channels.[2] TRP channels are Ca2+ permeable non-selective cation channels that play roles in a wide variety of physiological processes, including calcium signaling, heat and cold sensation, calcium and magnesium homeostasis. TRPMs mediates sodium and calcium entry, which induces depolarization and a cytoplasmic Ca2+ signal. Alternatively spliced transcript variants encoding different isoforms have been -identified.[3] TRPM3 was shown to be activated by the neurosteroid pregnenolone sulfate as well as the synthetic compound CIM0216.
Peripheral heat sensation
TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia, and they are activated by high temperatures.[4] Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as inflammatory thermal hyperalgesia.[4][5] Inhibitors of TRPM3 were also shown to reduce noxious heat and inflammatory heat hyperalgesia,[6][7][5] as well as reduce heat hyperalgesia and spontaneous pain in nerve injury induced neuropathic pain.[5]
Receptor mediated inhibition
TRPM3 is robustly inhibited by the activation of cell surface receptors that couple to inhibitory heterotrimeric G-proteins (Gi) via direct binding of the Gβγ subunit of the G-protein to the channel.[8][9][10] Gβγ was shown to bind to a short α-helical segment of the channel.[11] Receptors that inhibit TRPM3 include opioid receptors[9][12] and GABAB receptors.[8]
TRPM3 in the brain
Mutations in TRPM3 in humans, were recently shown to cause a intellectual disability and epilepsy.[13] The disease associated mutations were shown to increase the sensitivity of the channel to agonists, and heat.[14][15][16]
TRPM3 ligands, activators and modulators
Activators
Channel Blockers
- Mefenamic acid[19]
- Citrus fruit flavonoids, e.g. naringenin, isosakuranetin and hesperetin, as well as ononetin (a deoxybenzoin).[20]
- Primidone, a clinically used antiepileptic medication also directly inhibits TRPM3.[6]
Activity Modulator
- pH [21]
See also
- TRPM
- TRPM3-related neurodevelopmental disorders
References
- ↑ "International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels". Pharmacological Reviews 57 (4): 427–50. December 2005. doi:10.1124/pr.57.4.6. PMID 16382100.
- ↑ "An introduction to TRP channels". Annual Review of Physiology 68: 619–47. 2006. doi:10.1146/annurev.physiol.68.040204.100431. PMID 16460286.
- ↑ "Entrez Gene: TRPM3 transient receptor potential cation channel, subfamily M, member 3". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=80036.
- ↑ 4.0 4.1 4.2 "TRPM3 is a nociceptor channel involved in the detection of noxious heat". Neuron 70 (3): 482–94. May 2011. doi:10.1016/j.neuron.2011.02.051. PMID 21555074.
- ↑ 5.0 5.1 5.2 Su, Songxue; Yudin, Yevgen; Kim, Nawoo; Tao, Yuan-Xiang; Rohacs, Tibor (2021-03-17). "TRPM3 Channels Play Roles in Heat Hypersensitivity and Spontaneous Pain after Nerve Injury". The Journal of Neuroscience 41 (11): 2457–2474. doi:10.1523/JNEUROSCI.1551-20.2020. ISSN 1529-2401. PMID 33478988.
- ↑ 6.0 6.1 "Primidone inhibits TRPM3 and attenuates thermal nociception in vivo". Pain 158 (5): 856–867. May 2017. doi:10.1097/j.pain.0000000000000846. PMID 28106668.
- ↑ Straub, Isabelle; Krügel, Ute; Mohr, Florian; Teichert, Jens; Rizun, Oleksandr; Konrad, Maik; Oberwinkler, Johannes; Schaefer, Michael (November 2013). "Flavanones that selectively inhibit TRPM3 attenuate thermal nociception in vivo". Molecular Pharmacology 84 (5): 736–750. doi:10.1124/mol.113.086843. ISSN 1521-0111. PMID 24006495. https://pubmed.ncbi.nlm.nih.gov/24006495.
- ↑ 8.0 8.1 "Inhibition of Transient Receptor Potential Melastatin 3 ion channels by G-protein βγ subunits". eLife 6. August 2017. doi:10.7554/eLife.26147. PMID 28829742.
- ↑ 9.0 9.1 "Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels". eLife 6. August 2017. doi:10.7554/eLife.26280. PMID 28826482.
- ↑ "G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons". eLife 6. August 2017. doi:10.7554/eLife.26138. PMID 28826490.
- ↑ "The structural basis for an on-off switch controlling Gβγ-mediated inhibition of TRPM3 channels". Proceedings of the National Academy of Sciences of the United States of America 117 (46): 29090–29100. November 2020. doi:10.1073/pnas.2001177117. PMID 33122432. Bibcode: 2020PNAS..11729090B.
- ↑ "The G-protein-biased agents PZM21 and TRV130 are partial agonists of μ-opioid receptor-mediated signalling to ion channels". British Journal of Pharmacology 176 (17): 3110–3125. September 2019. doi:10.1111/bph.14702. PMID 31074038.
- ↑ "De novo substitutions of TRPM3 cause intellectual disability and epilepsy". European Journal of Human Genetics 27 (10): 1611–1618. October 2019. doi:10.1038/s41431-019-0462-x. PMID 31278393.
- ↑ "Disease-associated mutations in the human TRPM3 render the channel overactive via two distinct mechanisms". eLife 9. April 2020. doi:10.7554/eLife.55634. PMID 32343227.
- ↑ "Gain of channel function and modified gating properties in TRPM3 mutants causing intellectual disability and epilepsy". eLife 9. May 2020. doi:10.7554/eLife.57190. PMID 32427099.
- ↑ "The newest TRP channelopathy: Gain of function TRPM3 mutations cause epilepsy and intellectual disability". Channels 15 (1): 386–397. December 2021. doi:10.1080/19336950.2021.1908781. PMID 33853504.
- ↑ "Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic beta cells". Nature Cell Biology 10 (12): 1421–30. December 2008. doi:10.1038/ncb1801. PMID 18978782.
- ↑ "Activation of TRPM3 by a potent synthetic ligand reveals a role in peptide release". Proceedings of the National Academy of Sciences of the United States of America 112 (11): E1363-72. March 2015. doi:10.1073/pnas.1419845112. PMID 25733887. Bibcode: 2015PNAS..112E1363H.
- ↑ "Fenamates as TRP channel blockers: mefenamic acid selectively blocks TRPM3". British Journal of Pharmacology 162 (8): 1757–69. April 2011. doi:10.1111/j.1476-5381.2010.01186.x. PMID 21198543.
- ↑ "Citrus fruit and fabacea secondary metabolites potently and selectively block TRPM3". British Journal of Pharmacology 168 (8): 1835–50. April 2013. doi:10.1111/bph.12076. PMID 23190005.
- ↑ Hossain Saad Md Zubayer, Xiang Liuruimin, Liao Yan-Shin, Reznikov Leah R., Du Jianyang (2021). "The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons". Frontiers in Pharmacology 12:632711: 632711. doi:10.3389/fphar.2021.632711. PMID 33603674.
Further reading
- "TRPM3". Transient Receptor Potential (TRP) Channels. Handbook of Experimental Pharmacology. 179. 2007. pp. 253–67. doi:10.1007/978-3-540-34891-7_15. ISBN 978-3-540-34889-4.
- "TRP channels activated by extracellular hypo-osmoticity in epithelia". Biochemical Society Transactions 35 (Pt 1): 91–5. February 2007. doi:10.1042/BST0350091. PMID 17233610.
- "TRPM3 in temperature sensing and beyond". Temperature 2 (2): 201–13. 2014. doi:10.4161/23328940.2014.988524. PMID 27227024.
- Transient Receptor Potential Channels. Advances in Experimental Medicine and Biology. 704. New York: Springer Science+Business Media. 2011. doi:10.1007/978-94-007-0265-3. ISBN 978-94-007-0265-3. OCLC 710148029. http://trpbook.islets.se.
External links
- TRPM3+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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