Biology:KvLQT2
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Kv7.2 (KvLQT2) is a voltage- and lipid-gated potassium channel protein coded for by the gene KCNQ2.
It is associated with benign familial neonatal epilepsy.
Function
The M channel is a slowly activating and deactivating potassium channel that plays a critical role in the regulation of neuronal excitability. The M channel is formed by the association of the protein encoded by this gene and a related protein encoded by the KCNQ3 gene, both integral membrane proteins. M channel currents are inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 1 (BFNC), also known as epilepsy, benign neonatal type 1 (EBN1). At least five transcript variants encoding five different isoforms have been found for this gene.[1]
Ligands
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- ICA-069673: channel opener at KCNQ2/Q3, 20-fold selective over KCNQ3/Q5, no measurable activity against a panel of cardiac ion channels (hERG, Nav1.5, L type channels, and KCNQ1) and no activity on GABAA gated channels at 10 μM. A range of related benzamides exhibited activity, of which compound number 40 is shown here.[2]
- ML252: channel inhibitor, IC50 = 70nM.[3]
- Phosphatidylinositol 4,5-bisphosphate (PIP2)
References
- ↑ "Entrez Gene: KCNQ2 potassium voltage-gated channel, KQT-like subfamily, member 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3785.
- ↑ "N -Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy". ACS Medicinal Chemistry Letters 2 (6): 481–484. 2011. doi:10.1021/ml200053x. PMID 24900334.
- ↑ "Discovery of a series of 2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)acetamides as novel molecular switches that modulate modes of K(v)7.2 (KCNQ2) channel pharmacology: identification of (S)-2-phenyl-N-(2-(pyrrolidin-1-yl)phenyl)butanamide (ML252) as a potent, brain penetrant K(v)7.2 channel inhibitor". Journal of Medicinal Chemistry 55 (15): 6975–9. August 2012. doi:10.1021/jm300700v. PMID 22793372.
Further reading
- "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacological Reviews 57 (4): 473–508. December 2005. doi:10.1124/pr.57.4.10. PMID 16382104.
- "Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles". DNA Research 3 (5): 311–20. October 1996. doi:10.1093/dnares/3.5.311. PMID 9039501.
- "A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns". Nature Genetics 18 (1): 25–9. January 1998. doi:10.1038/ng0198-25. PMID 9425895.
- "A potassium channel mutation in neonatal human epilepsy". Science 279 (5349): 403–6. January 1998. doi:10.1126/science.279.5349.403. PMID 9430594. Bibcode: 1998Sci...279..403B.
- "Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy". The Journal of Biological Chemistry 273 (31): 19419–23. July 1998. doi:10.1074/jbc.273.31.19419. PMID 9677360.
- "The KCNQ2 potassium channel: splice variants, functional and developmental expression. Brain localization and comparison with KCNQ3". FEBS Letters 438 (3): 171–6. November 1998. doi:10.1016/S0014-5793(98)01296-4. PMID 9827540.
- "KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel". Science 282 (5395): 1890–3. December 1998. doi:10.1126/science.282.5395.1890. PMID 9836639. Bibcode: 1998Sci...282.1890W.
- "Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy". Nature 396 (6712): 687–90. December 1998. doi:10.1038/25367. PMID 9872318. Bibcode: 1998Natur.396..687S.
- "Structural and mutational analysis of KCNQ2, the major gene locus for benign familial neonatal convulsions". Human Genetics 104 (3): 234–40. March 1999. doi:10.1007/PL00008713. PMID 10323247.
- "Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell". The Journal of Neuroscience 19 (18): 7742–56. September 1999. doi:10.1523/jneurosci.19-18-07742.1999. PMID 10479678. PMC 6782456. http://discovery.ucl.ac.uk/22399/4/Brown_Two%20Types%20of%20K%E2%81%BA%20Channel%20Subunit%2C%20Erg1%20and%20KCNQ23%2C%20Contribute%20to%20the%20M-Like%20Current%20in%20a%20Mammalian%20Neuronal%20Cell_VoR.pdf.
- "Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current". The Journal of Neuroscience 20 (5): 1710–21. March 2000. doi:10.1523/jneurosci.20-05-01710.2000. PMID 10684873.
- "The novel anticonvulsant retigabine activates M-currents in Chinese hamster ovary-cells tranfected with human KCNQ2/3 subunits". Neuroscience Letters 282 (1–2): 73–6. March 2000. doi:10.1016/S0304-3940(00)00866-1. PMID 10713399.
- "Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptors". The Journal of Physiology 522 (3): 349–55. February 2000. doi:10.1111/j.1469-7793.2000.t01-2-00349.x. PMID 10713961.
- "Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy". Proceedings of the National Academy of Sciences of the United States of America 97 (9): 4914–9. April 2000. doi:10.1073/pnas.090092797. PMID 10781098. Bibcode: 2000PNAS...97.4914C.
- "Surface expression and single channel properties of KCNQ2/KCNQ3, M-type K+ channels involved in epilepsy". The Journal of Biological Chemistry 275 (18): 13343–8. May 2000. doi:10.1074/jbc.275.18.13343. PMID 10788442.
- "Modulation of KCNQ2/3 potassium channels by the novel anticonvulsant retigabine". Molecular Pharmacology 58 (2): 253–62. August 2000. doi:10.1124/mol.58.2.253. PMID 10908292.
- "Retigabine, a novel anti-convulsant, enhances activation of KCNQ2/Q3 potassium channels". Molecular Pharmacology 58 (3): 591–600. September 2000. doi:10.1124/mol.58.3.591. PMID 10953053.
- "M-type KCNQ2-KCNQ3 potassium channels are modulated by the KCNE2 subunit". FEBS Letters 480 (2–3): 137–41. September 2000. doi:10.1016/S0014-5793(00)01918-9. PMID 11034315.
- "Differential expression of kcnq2 splice variants: implications to m current function during neuronal development". The Journal of Neuroscience 21 (4): 1096–103. February 2001. doi:10.1523/jneurosci.21-04-01096.2001. PMID 11160379.
- "Benign familial neonatal convulsions (BFNC) resulting from mutation of the KCNQ2 voltage sensor". European Journal of Human Genetics 8 (12): 994–7. December 2000. doi:10.1038/sj.ejhg.5200570. PMID 11175290.
External links
- KCNQ2+Potassium+Channel 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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