TRPM3

TRPM3
Identifiers
Aliases	TRPM3, GON-2, LTRPC3, MLSN2, transient receptor potential cation channel subfamily M member 3
External IDs	OMIM: 608961; MGI: 2443101; HomoloGene: 62287; GeneCards: TRPM3; OMA:TRPM3 - orthologs
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q21.12-q21.13 Start 70,529,060 bp[1] End 71,446,904 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 B Start 22,116,410 bp[2] End 22,972,774 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium internal globus pallidus sural nerve inferior olivary nucleus external globus pallidus cerebellar vermis superior vestibular nucleus Brodmann area 23 pons endothelial cell Top expressed in retinal pigment epithelium ciliary body otolith organ utricle median eminence cerebellar vermis superior colliculus habenula inferior colliculus pineal gland More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ion channel activity calcium activated cation channel activity cation channel activity calcium channel activity Cellular component integral component of membrane plasma membrane membrane Biological process detection of temperature stimulus ion transport protein tetramerization sensory perception of temperature stimulus calcium ion transport ion transmembrane transport cation transport transmembrane transport calcium ion transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 80036 226025 Ensembl ENSG00000083067 ENSMUSG00000052387 UniProt Q9HCF6 n/a RefSeq (mRNA) NM_001007470 NM_001007471 NM_020952 NM_024971 NM_206944 NM_206945 NM_206946 NM_206947 NM_206948 NM_001366141 NM_001366142 NM_001366143 NM_001366144 NM_001366145 NM_001366146 NM_001366147 NM_001366148 NM_001366149 NM_001366150 NM_001366151 NM_001366152 NM_001366153 NM_001366154 NM_001035239 NM_001035240 NM_001035241 NM_001035242 NM_001035243 NM_001035244 NM_001035245 NM_001035246 NM_177341 NM_001362487 NM_001362488 NM_001362489 NM_001362490 NM_001362491 NM_001362496 NM_001362497 NM_001362498 NM_001362499 NM_001362500 NM_001362501 NM_001362502 NM_001362503 NM_001362504 NM_001362505 NM_001362506 NM_001362507 NM_001362508 NM_001362511 NM_001362512 NM_001362513 RefSeq (protein) NP_001007471 NP_001007472 NP_066003 NP_079247 NP_996827 NP_996828 NP_996829 NP_996830 NP_996831 NP_001353070 NP_001353071 NP_001353072 NP_001353073 NP_001353074 NP_001353075 NP_001353076 NP_001353077 NP_001353078 NP_001353079 NP_001353080 NP_001353081 NP_001353082 NP_001353083 n/a Location (UCSC) Chr 9: 70.53 – 71.45 Mb Chr 19: 22.12 – 22.97 Mb PubMed search [3] [4]
Wikidata
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Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the TRPM3 gene.^[5]

Function

The product of this gene belongs to the family of transient receptor potential (TRP) channels.^[6] 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.^[7] 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.^[8] Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as inflammatory thermal hyperalgesia.^[8][9] Inhibitors of TRPM3 were also shown to reduce noxious heat and inflammatory heat hyperalgesia,^[10][11][9] as well as reduce heat hyperalgesia and spontaneous pain in nerve injury induced neuropathic pain.^[9]

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.^[12][13][14] Gβγ was shown to bind to a short α-helical segment of the channel.^[15] Receptors that inhibit TRPM3 include opioid receptors^[13][16] and GABA_B receptors.^[12]

TRPM3 in the brain

Mutations in TRPM3 in humans, were recently shown to cause a intellectual disability and epilepsy.^[17] The disease associated mutations were shown to increase the sensitivity of the channel to agonists, and heat.^[18][19][20]

TRPM3 ligands, activators and modulators

Activators

• Heat^[8]
• Pregnenolone Sulfate^[21]
• CIM-0216^[22]

Channel Blockers

1. Mefenamic acid^[23]
2. Citrus fruit flavonoids, e.g. naringenin, isosakuranetin and hesperetin, as well as ononetin (a deoxybenzoin).^[24]
3. Primidone, a clinically used antiepileptic medication also directly inhibits TRPM3.^[10]

Activity Modulator

• pH ^[25]

See also

• TRPM
• TRPM3-related neurodevelopmental disorders

References

Further reading

External links

• TRPM3+protein,+human at the U.S. 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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