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TRPM
TRPM is a family of transient receptor potential ion channels (''M'' standing for '' wikt:melastatin''). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8. 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. *TRPM4 and TRPM5 are activated by intrace ...
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Transient Receptor Potential Channel
Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TRPV ("V" for vanilloid), TRPVL ("VL" for vanilloid-like), TRPM ("M" for melastatin), TRPS ("S" for soromelastatin), TRPN ("N" for no mechanoreceptor potential C), and TRPA ("A" for ankyrin). Group 2 consists of TRPP ("P" for polycystic) and TRPML ("ML" for mucolipin). Other less-well categorized TRP channels exist, including yeast channels and a number of Group 1 and Group 2 channels present in non-animals. Many of these channels mediate a variety of sensations such as pain, temperature, different kinds of tastes, pressure, and vision. In the body, some TRP channels are thought to behave like microscopic thermometers and used in animals to sense hot or cold. Some TRP channels are activated by molecules found in spices like garlic (alli ...
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TRPM8
Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), also known as the cold and menthol receptor 1 (CMR1), is a protein that in humans is encoded by the ''TRPM8'' gene. The TRPM8 channel is the primary molecular transducer of cold somatosensation in humans. In addition, mints can desensitize a region through the activation of TRPM8 receptors (the 'cold'/menthol receptor). Structure The TRPM8 channel is a homotetramer, composed of four identical subunits with a transmembrane domain with six helices (S1–6). The first four, S1–4, act as the voltage sensor and allow binding of menthol, icilin and similar channel agonists. S5 and S6 and a connecting loop, also part of the structure, make up the pore, a non-selective cation channel which consists of a highly conserved hydrophobic region. A range of diverse components are required for the high level of specificity in response to cold and menthol stimuli which eventually lead to ion flow through ...
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TRPM5
Transient receptor potential cation channel subfamily M member 5 (TRPM5), also known as long transient receptor potential channel 5 is a protein that in humans is encoded by the ''TRPM5'' gene. Function TRPM5 is a calcium-activated non-selective cation channel that induces depolarization upon increases in intracellular calcium, it is a signal mediator in chemosensory cells. Channel activity is initiated by a rise in the intracellular calcium, and the channel permeates monovalent cations as K+ and Na+. TRPM5 is a key component of taste transduction in the gustatory system of bitter, sweet and umami tastes being activated by high levels of intracellular calcium. It has also been targeted as a possible contributor to fat taste signaling. The calcium dependent opening of TRPM5 produces a depolarizing generator potential which leads to an action potential. TRPM5 is expressed in pancreatic β-cells where it is involved in the signaling mechanism for insulin secretion. The potentia ...
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TRPM3
Transient receptor potential cation channel subfamily M member 3 is a protein that in humans is encoded by the ''TRPM3'' gene. Function The product of this gene belongs to the family of transient receptor potential (TRP) channels. 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. 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. Genetic deletion of TRPM3 in mice reduces sensitivity to noxious heat, as well as ...
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TRPM2
Transient receptor potential cation channel, subfamily M, member 2, also known as TRPM2, is a protein that in humans is encoded by the ''TRPM2'' gene. Structure The protein encoded by this gene is a non-selective calcium-permeable cation channel and is part of the Transient Receptor Potential ion channel super family. The closest relative is the cold and menthol activated TRPM8 ion channel. While TRPM2 is not cold sensitive it is activated by heat. The TRPM2 ion channel is activated by free intracellular ADP-ribose in synergy with free intracellular calcium. ADP-Ribose is produced to by the enzyme PARP in response to oxidative stress and confers susceptibility to cell death. Several alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. Function The ''TRPM2'' gene is highly expressed in the brain and was implicated by both genetic linkage studies in families and then by case control or trio allelic association stu ...
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TRPM1
Transient receptor potential cation channel subfamily M member 1 is a protein that in humans is encoded by the ''TRPM1'' gene. Function The protein encoded by this gene is a member of the transient receptor potential (TRP) family of non-selective cation channels. It is expressed in the retina, in a subset of bipolar cells termed ON bipolar cells. These cells form synapses with either rods or cones, collecting signals from them. In the dark, the signal arrives in the form of the neurotransmitter glutamate, which is detected by a G protein-coupled receptor (GPCR) signal transduction cascade. Detection of glutamate by the GPCR Metabotropic glutamate receptor 6 results in closing of the TRPM1 channel. At the onset of light, glutamate release is halted and mGluR6 is deactivated; this results in opening of the TRPM1 channel, influx of sodium and calcium, and depolarization of the bipolar cell. In addition to the retina, TRPM1 is also expressed in melanocytes, which are melanin-p ...
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TRPM4
Transient receptor potential cation channel subfamily M member 4 (hTRPM4), also known as melastatin-4, is a protein that in humans is encoded by the TRPM4 gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a .... TRPM4 Channel Blocker * 9-Phenanthrol * TRPM4-IN-5 See also * TRPM References Further reading * * * * * * External links * Ion channels {{membrane-protein-stub ...
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TRPM7
Transient receptor potential cation channel, subfamily M, member 7, also known as TRPM7, is a human gene encoding a protein of the same name. Function TRPs, mammalian homologs of the Drosophila transient receptor potential (trp) protein, are ion channels that are thought to mediate capacitative calcium entry into the cell. TRP-PLIK is a protein that is both an ion channel and a kinase. As a channel, it conducts calcium and monovalent cations to depolarize cells and increase intracellular calcium. As a kinase, it is capable of phosphorylating itself and other substrates. The kinase activity is necessary for channel function, as shown by its dependence on intracellular ATP and by the kinase mutants. upplied by OMIMref> Interactions TRPM7 has been shown to interact with PLCB1 and PLCB2. Clinical relevance Defects in this gene have been associated to magnesium deficiency in human microvascular endothelial cells. See also * TRPM TRPM is a family of transient recept ...
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TRPM6
TRPM6 is a transient receptor potential ion channel associated with hypomagnesemia with secondary hypocalcemia. See also * TRPM TRPM is a family of transient receptor potential ion channels (''M'' standing for '' wikt:melastatin''). Functional TRPM channels are believed to form tetramers. The TRPM family consists of eight different channels, TRPM1–TRPM8. Unlike the TRP ... * Ruthenium red References Further reading * * * * External links * Ion channels {{membrane-protein-stub ...
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Ion Channel
Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters. The study of ion channels often involves biophysics, electrophysiology, and pharmacology, while using techniques including voltage clamp, patch clamp, immunohistochemistry, X-ray crystallography, fluoroscopy, and RT-PCR. Their classification as molecules is referred to as channelomics. Basic features There are two distinctive features of ion channels that differentiate them from other types of ion transporter proteins: #The rate of ion transport t ...
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Adenosine 5'-diphosphoribose
Adenosine diphosphate ribose (ADPR) is an ester molecule formed into chains by the enzyme poly ADP ribose polymerase. ADPR is created from cyclic ADP-ribose (cADPR) by the CD38 enzyme using nicotinamide adenine dinucleotide (NAD+) as a cofactor. ADPR binds to and activates the TRPM2 ion channel. ADPR is the most potent agonist of the TRPM2 channel. cADPR also binds to TPRM2, and the action of both molecules is synergistic, with both molecules enhancing the action of the other molecule in activating the TRPM2 channel. See also * Adenosine diphosphate * ADP-ribosylation * Ribose Ribose is a simple sugar and carbohydrate with molecular formula C5H10O5 and the linear-form composition H−(C=O)−(CHOH)4−H. The naturally-occurring form, , is a component of the ribonucleotides from which RNA is built, and so this com ... References Nucleotides Organophosphates NADH dehydrogenase inhibitors Phosphate esters {{biochemistry-stub ...
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Icilin
Icilin (AG-3-5) is a synthetic super-agonist of the transient receptor potential M8 (TRPM8) ion channel. Although structurally not related with menthol, it produces an extreme sensation of cold, both in humans and animals. It is almost 200 times more potent than menthol, and 2.5 times more efficacious. Despite their similar effects, icilin activates the TRPM8 receptor in a different way to menthol. Icilin has been shown to be effective in the treatment of pruritus in an experimental model of itch. It is now used as a research tool for the study of TRP channels Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), T ..., although despite its high potency it is less selective for TRPM8 over other related ion channels than newer compounds such as WS-12. References External links Product ...
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