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Ion Channel Family
The transmembrane cation channel superfamily was defined in InterPro and Pfam as the family of tetrameric ion channels. These include the sodium, potassium, calcium, ryanodine receptor, HCN, CNG, CatSper, and TRP channels. This large group of ion channels apparently includes families , , , and of the TCDB transporter classification. They are described as minimally having two transmembrane helices flanking a loop which determines the ion selectivity of the channel pore. Many eukaryotic channels have four additional transmembrane helices (TM) (), related to or vestigial of voltage gating. The proteins with only two transmembrane helices () are most commonly found in bacteria. This also includes the 2-TM inward-rectifier potassium channels () found primarily in eukaryotes. There are commonly additional regulatory domains which serve to regulate ion conduction and channel gating. The pores may also be homotetramers or heterotetramers; where heterotetramers may be encoded ...
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Lipid Bilayer
The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, and membranes of the membrane-bound organelles in the cell. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role, even though they are only a few nanometers in width, because they are impermeable to most water-soluble (hydrophilic) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps. Biological bilayers are usually composed of amphiphilic phosphol ...
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Voltage-gated Ion Channel
Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, betwee ...
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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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TRPC7
Transient receptor potential cation channel, subfamily C, member 7, also known as TRPC7, is a human gene encoding a protein of the same name. See also * TRPC TRPC is a family of transient receptor potential cation channels in animals. TRPC channels form the subfamily of channels in humans most closely related to drosophila TRP channels. Structurally, members of this family possess a number of similar ... Further reading * * * External links * Ion channels {{membrane-protein-stub ...
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TRPC6
Transient receptor potential cation channel, subfamily C, member 6, also known as TRPC6, is a human gene encoding a protein of the same name. TRPC6 is a transient receptor potential channel of the classical TRPC subfamily. It has been associated with depression and anxiety (see below), as well as with focal segmental glomerulosclerosis (FSGS). Interactions TRPC6 has been shown to interact with: * FYN, * TRPC2, and * TRPC3. Ligands Two of the primary active constituents responsible for the antidepressant and anxiolytic benefits of '' Hypericum perforatum'', also known as St. John's Wort, are hyperforin and adhyperforin. These compounds are inhibitors of the reuptake of serotonin, norepinephrine, dopamine, γ-aminobutyric acid, and glutamate, and they are reported to exert these effect Effect may refer to: * A result or change of something ** List of effects ** Cause and effect, an idiom describing causality Pharmacy and pharmacology * Drug effect, a change r ...
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TRPC5
Short transient receptor potential channel 5 (TrpC5) also known as transient receptor protein 5 (TRP-5) is a protein that in humans is encoded by the ''TRPC5'' gene. TrpC5 is subtype of the TRPC family of mammalian transient receptor potential ion channels. Function TrpC5 is one of the seven mammalian TRPC (transient receptor potential canonical) proteins. TrpC5 is a multi-pass membrane protein and is thought to form a receptor-activated non-selective calcium permeant cation channel. The protein is active alone or as a heteromultimeric assembly with TRPC1, TRPC3, and TRPC4. It also interacts with multiple proteins including calmodulin, CABP1, enkurin, Na+–H+ exchange regulatory factor (NHERF), interferon-induced GTP-binding protein (MX1), ring finger protein 24 ( RNF24), and SEC14 domain and spectrin repeat-containing protein 1 ( SESTD1). TRPC4 and TRPC5 have been implicated in the mechanism of mercury toxicity and neurological behavior. It was established in 2021 that ...
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TRPC4
The short transient receptor potential channel 4 (TrpC4), also known as Trp-related protein 4, is a protein that in humans is encoded by the ''TRPC4'' gene. Function TrpC4 is a member of the transient receptor potential cation channels. This protein forms a non-selective calcium-permeable cation channel that is activated by Gαi-coupled receptors, Gαq- coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Tissue distribution The nonselective cation channel TrpC4 has been shown to be present in high abundance in the cortico- limbic regions of the brain. In addition, TRPC4 mRNA is present in midbrain dopaminergic neurons in the ventral tegmental area and the substantia nigra. Roles Deletion of the ''trpc4'' gene decreases levels of sociability in a social exploration task. These results suggest that TRPC4 may play a role in regulating social anx ...
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TRPC3
Short transient receptor potential channel 3 (TrpC3) also known as transient receptor protein 3 (TRP-3) is a protein that in humans is encoded by the TRPC3 gene. The TRPC3/6/7 subfamily are implicated in the regulation of vascular tone, cell growth, proliferation and pathological hypertrophy. These are diacylgylcerol-sensitive cation channels known regulate intracellular calcium via activation of the phospholipase C (PLC) pathway and/or by sensing Ca2+ store depletion. Together, their role in calcium homeostasis has made them potential therapeutic targets for a variety of central and peripheral pathologies. Function Non-specific cation conductance elicited by the activation of TrkB by BDNF is TRPC3-dependent in the CNS. TRPC channels are almost always co-localized with mGluR1-expressing cells and likely play a role in mGluR-mediated EPSPs. The TRPC3 channel has been shown to be preferentially expressed in non-excitable cell types, such as oligodendrocytes. However, evidence ...
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TRPC1
Transient receptor potential canonical 1 (TRPC1) is a protein that in humans is encoded by the ''TRPC1'' gene. Function TRPC1 is an ion channel located on the plasma membrane of numerous human and animal cell types. It is a nonspecific cation channel, which means that both sodium and calcium ions can pass through it. TRPC1 is thought to mediate calcium entry in response to depletion of endoplasmic calcium stores or activation of receptors coupled to the phospholipase C system. In HEK293 cells the unitary current-voltage relationship of endogenous TRPC1 channels is almost linear, with a slope conductance of about 17 pS. The extrapolated reversal potential of TRPC1 channels is +30 mV. The TRPC1 protein is widely expressed throughout the mammalian brain and has a similar corticolimbic expression pattern as TRPC4 and TRPC5. The highest density of TRPC1 protein is found in the lateral septum, an area with dense TRPC4 expression, and hippocampus and prefrontal cortex, areas with de ...
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TPTE
Putative tyrosine-protein phosphatase TPTE is an enzyme that in humans is encoded by the ''TPTE'' gene. Function TPTE is a member of a large class of membrane-associated phosphatases with substrate specificity for the 3-position phosphate of inositol phospholipid Phospholipids, are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...s. TPTE is a primate-specific duplicate of the TPTE2 (TPIP) inositol phospholipd phosphatase; TPTE itself is predicted to lack phosphatase activity. TPTE and TPTE2 are the mammalian homologues to the subfamily of voltage sensitive phosphatases. References Further reading

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HVCN1
Voltage-gated hydrogen channel 1 is a protein that in humans is encoded by the HVCN1 gene. Voltage-gated hydrogen channel 1 is a voltage-gated proton channel that has been shown to allow proton transport into phagosomes and out of many types of cells including spermatozoa, electrically excitable cells and respiratory epithelial cells. The proton-conducting HVCN1 channel has only transmembrane domains corresponding to the S1-S4 voltage sensing domains (VSD) of voltage-gated potassium channels and voltage-gated sodium channels. Molecular simulation is consistent with a water-filled pore that can function as a " water wire" for allowing hydrogen bonded H+ to cross the membrane. However, mutation of Asp112 in human Hv1 results in anion permeation, suggesting that obligatory protonation of Asp produces proton selectivity. Quantum mechanical calculations show that the Asp-Arg interaction can produce proton selective permeation. The HVCN1 protein has been shown to exist as a dimer wi ...
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