TRPM

Family of transport proteins

TRPM is a family of transient receptor potential ion channels (M standing for wikt:melastatin).^[1] Functional TRPM channels are believed to form tetramers.^[2] The TRPM family consists of eight different channels, TRPM1–TRPM8.^[3]

Unlike the TRPC and TRPV sub-families, TRPM subunits do not contain N-terminal ankyrin repeat motifs but, rather, contain entire functional proteins in their C-termini. TRPM6 and TRPM7, for example, contain functional α-kinase segments, which are a type of serine/threonine-specific protein kinase.

Permeability and activation

The relative permeability of calcium and magnesium varies widely among TRPM channels.

TRPM4 and TRPM5 are impermeable to calcium.
TRPM3, TRPM6 and TRPM7 are highly permeable to both calcium and magnesium.

The mechanism of activation also varies greatly among TRPM channels.

TRPM2 is activated by ADP-ribose adenosine 5'-diphosphoribose and functions as a sensor of redox status in cells.^[4]
TRPM4 and TRPM5 are activated by intracellular calcium.
TRPM8 can be activated by low temperatures, menthol, eucalyptol and icilin.^[5]^[6]

Functions

Among the functional responsibilities of the TRPM channels are:

regulation of calcium oscillations after T cell activation^[7] and prevention of cardiac conduction disorders (TRPM4).^[8]
modulation of insulin secretion and sensory transduction in taste cells (TRPM5).^[9]
cold sensation (TRPM8).
heat sensation and inflammatory pain (TRPM3).^[10]
regulation of magnesium reabsorption in the kidneys and absorption in the intestines (TRPM6).^[11]
regulation of cell adhesion (TRPM7).^[12]

Genes

TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8

References

^ Kraft R, Harteneck C (2005). "The mammalian melastatin-related transient receptor potential cation channels: an overview". Pflügers Arch. 451 (1): 204–211. doi:10.1007/s00424-005-1428-0. PMID 15895246. S2CID 22823024.
^ Jiang LH (2007). "Subunit interaction in channel assembly and functional regulation of transient receptor potential melastatin (TRPM) channels". Biochem Soc Trans. 35 (1): 86–8. doi:10.1042/BST0350086. PMID 17233608.
^ Boesmans W, Owsianik G, Tack J, Voets T, Vanden Berghe P (2011). "TRP channels in neurogastroenterology: opportunities for therapeutic intervention". British Journal of Pharmacology. 162 (1): 18–37. doi:10.1111/j.1476-5381.2010.01009.x. PMC 3012403. PMID 20804496.
^ Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y (2002). "LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death". Mol Cell. 9 (1): 163–173. doi:10.1016/S1097-2765(01)00438-5. PMID 11804595.
^ Behrendt HJ, Germann T, Gillen C, Hatt H, Jostock R (2004). "Characterization of the mouse cold-menthol receptor TRPM8 and vanilloid receptor type-1 VR1 using a fluorometric imaging plate reader (FLIPR) assay". Br. J. Pharmacol. 141 (4): 737–745. doi:10.1038/sj.bjp.0705652. PMC 1574235. PMID 14757700.
^ Nilius B, Owsianik G, Voets T, Peters JA (2007). "Transient receptor potential cation channels in disease" (PDF). Physiol. Rev. 87 (1): 165–217. doi:10.1152/physrev.00021.2006. PMID 17237345.
^ Launay P, Cheng H, Srivatsan S, Penner R, Fleig A, Kinet J-P (2004). "TRPM4 regulates calcium oscillations after T cell activation". Science. 306 (5700): 1374–1377. doi:10.1126/science.1098845. PMID 15550671. S2CID 16459097.
^ Mathar, I; Jacobs, G; Kecskes, M; Menigoz, A; Philippaert, K; Vennekens, R (2014). TRPM4. Handbook of Experimental Pharmacology. Vol. 222. pp. 461–87. doi:10.1007/978-3-642-54215-2_18. ISBN 978-3-642-54214-5. PMID 24756717.
^ Philippaert, K; Pironet, A; Mesuere, M; Sones, W; Vermeiren, L; Kerselaers, S; Pinto, S; Segal, A; Antoine, N; Gysemans, C; Laureys, J; Lemaire, K; Gilon, P; Cuypers, E; Tytgat, J; Mathieu, C; Schuit, F; Rorsman, P; Talavera, K; Voets, T; Vennekens, R (31 March 2017). "Steviol glycosides enhance pancreatic beta-cell function and taste sensation by potentiation of TRPM5 channel activity". Nature Communications. 8: 14733. doi:10.1038/ncomms14733. PMC 5380970. PMID 28361903.
^ Held, K; Voets, T; Vriens, J (2014). "TRPM3 in temperature sensing and beyond". Temperature (Austin, Tex.). 2 (2): 201–13. doi:10.4161/23328940.2014.988524. PMC 4844244. PMID 27227024.
^ Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D, Syrrou M, Nielsen S, Sassen M, Waldegger S, Seyberth HW, Konrad M (2002). "Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family". Nat. Genet. 31 (2): 166–170. doi:10.1038/ng889. PMID 12032568. S2CID 40990544.
^ Su L-T, Agapito MA, Li M, Simonson WTN, Huttenlocher A, Habas R, Yue L, Runnels LW (2006). "TRPM7 regulates cell adhesion by controlling the calcium-dependent protease calpain". J. Biol. Chem. 281 (16): 11260–11270. doi:10.1074/jbc.M512885200. PMC 3225339. PMID 16436382.

External links

TRPM+Cation+Channels at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
"Transient Receptor Potential Channels". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
"TRIP Database". a manually curated database of protein-protein interactions for mammalian TRP channels.

Membrane transport protein: ion channels (TC 1A)

Ca²⁺: Calcium channel

Ligand-gated	Inositol trisphosphate receptor 1 2 3 Ryanodine receptor 1 2 3
Voltage-gated	L-type/Ca_vα 1.1 1.2 1.3 1.4 N-type/Ca_vα2.2 P-type/Ca_vα 2.1 Q-type/Ca_vα2.1 R-type/Ca_vα2.3 T-type/Ca_vα 3.1 3.2 3.3 α₂δ-subunits 1 2 β-subunits β1 β2 β3 β4 γ-subunits γ1 γ2 γ3 γ4 Cation channels of sperm 1 2 3 4 Two-pore channel 1 2

Na⁺: Sodium channel

Constitutively active	Epithelial sodium channel α β γ δ
Proton-gated	Amiloride-sensitive cation channel 1 2 3 4
Voltage-gated	Na_vα 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 1.9 7A Na_vβ 1 2 3 4

K⁺: Potassium channel

Calcium-activated	BK channel α1 β1 β2 β3 β4 SK channel SK1 SK2 SK3 IK channel IK1 K_Ca 1.1 2.1 2.2 2.3 3.1 4.1 4.2 5.1
Inward-rectifier	K_ATP K_ir 1.1 2.1 2.2 2.3 2.4 2.6 GIRK/K_ir 3.1 3.2 3.3 3.4 K_ir 4.1 4.2 5.1 6.1 6.2 7.1
Tandem pore domain	K2P 1 2 3 4 5 6 7 9 10 12 13 15 16 17 18
Voltage-gated	K_vα1-6 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 2.1 2.2 3.1 3.2 3.3 3.4 4.1 4.2 4.3 5.1 6.1 6.2 6.3 6.4 K_vα7-12 7.1 7.2 7.3 7.4 7.5 8.1 8.2 9.1 9.2 9.3 10.1 10.2 11.1/hERG 11.2 11.3 12.1 12.2 12.3 K_vβ 1 2 3 KCNIP 1 2 3 4 minK/ISK minK/ISK-like MiRP 1 2 3 Shaker (gene)

Miscellaneous

Cl⁻: Chloride channel	Calcium-activated chloride channels Anoctamin ANO1 Bestrophin 1 2 Chloride Channel Accessory 1 2 3 4 CFTR CLCN 1 2 3 4 5 6 7 KA KB CLIC 1 2 3 4 5 6 L1 CLNS 1A 1B
H⁺: Proton channel	HVCN1
M⁺: CNG cation channel	α 1 2 3 4 β 1 2 3 HCN FC 1 2 3 4
M⁺: TRP cation channel	TRPA (1) TRPC 1 2 3 4 4AP 5 6 7 TRPM 1 2 3 4 5 6 7 8 TRPML 1 2 3 TRPN TRPP 1 2 TRPV 1 2 3 4 5 6
H₂O (+ solutes): Porin	Aquaporin 0 1 2 3 4 5 6 7 8 9 Voltage-dependent anion channel 1 2 3 General bacterial porin family
Cytoplasm: Gap junction	Connexin A GJA1 GJA3 GJA4 GJA5 GJA8 GJA9 GJA10 B GJB1 GJB2 GJB3 GJB4 GJB5 GJB6 GJB7 C GJC1 GJC2 GJC3 D GJD2 GJD3 GJD4 Innexin

By gating mechanism

Ion channel class	Ligand-gated Light-gated Voltage-gated Stretch-activated

see also disorders

TRP channel modulators

TRPA

Activators

4-Hydroxynonenal
4-Oxo-2-nonenal
4,5-EET
12S-HpETE
15-Deoxy-Δ^12,14-prostaglandin J2
α-Sanshool (ginger, Sichuan and melegueta peppers)
Acrolein
Allicin (garlic)
Allyl isothiocyanate (mustard, radish, horseradish, wasabi)
AM404
ASP-7663
Bradykinin
Cannabichromene (cannabis)
Cannabidiol (cannabis)
Cannabigerol (cannabis)
Cinnamaldehyde (cinnamon)
CR gas (dibenzoxazepine; DBO)
CS gas (2-chlorobenzal malononitrile)
Cuminaldehyde (cumin)
Curcumin (turmeric)
Dehydroligustilide (celery)
Diallyl disulfide
Dicentrine (Lindera spp.)
Farnesyl thiosalicylic acid
Formalin
Gingerols (ginger)
Hepoxilin A3
Hepoxilin B3
Hydrogen peroxide
Icilin
Isothiocyanate
JT-010
Ligustilide (celery, Angelica acutiloba)
Linalool (Sichuan pepper, thyme)
Methylglyoxal
Methyl salicylate (wintergreen)
N-Methylmaleimide
Nicotine (tobacco)
Oleocanthal (olive oil)
Paclitaxel (Pacific yew)
Paracetamol (acetaminophen)
PF-4840154
Phenacyl chloride
Polygodial (Dorrigo pepper)
Shogaols (ginger, Sichuan and melegueta peppers)
Tear gases
Tetrahydrocannabinol (cannabis)
Tetrahydrocannabiorcol
Thiopropanal S-oxide (onion)
Umbellulone (Umbellularia californica)
WIN 55,212-2

Blockers

TRPC

Activators	Adhyperforin (St John's wort) Diacyl glycerol GSK1702934A Hyperforin (St John's wort) Substance P
Blockers	DCDPC DHEA-S Flufenamic acid GSK417651A GSK2293017A Meclofenamic acid N-(p-Amylcinnamoyl)anthranilic acid Niflumic acid Pregnenolone sulfate Progesterone Pyr3 Tolfenamic acid