Biology:KCNK2
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Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the KCNK2 gene.[1][2][3]
This gene encodes K2P2.1, a lipid-gated ion channel belonging to the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that releases potassium out of the cell to control resting membrane potential. The channel is opened by anionic lipid, certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene.[3]
Function in neurons
TREK-1 is part of the subfamily of mechano-gated potassium channels that are present in mammalian neurons. They can be gated in both chemical and physical ways and can be opened via both physical stimuli and chemical stimuli. TREK-1 channels are found in a variety of tissues, but are particularly abundant in the brain and heart and are seen in various types of neurons.[4] The C-terminal of TREK-1 channels plays a role in the mechanosensitivity of the channels.[5]
In the neurons of the central nervous system, TREK-1 channels are important in physiological, pathophysiological, and pharmacological processes, including having a role in electrogenesis, ischemia, and anesthesia. TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal cord ischemia and is being evaluated as a potential target for new developments of therapeutic agents for neurology and anesthesiology.[6]
In the absence of a properly functioning cytoskeleton, TREK-1 channels can still open via mechanical gating.[5] The cell membrane functions independently of the cytoskeleton and the thickness and curvature of the membrane is able to modulate the activity of the TREK-1 channels.[7] The change in thickness is thought to be sensed by an amphipathic helix that extends from the inner leaflet of the membrane.[8]
The insertion of certain compounds into the membrane, including inhaled anesthetics and propofol, activate TREK-1 through the enzyme phospholipase D2 (PLD2). Prior to the addition of anesthetic, PLD2 associates with GM-1 lipid rafts. After anesthetic, the enzyme or a complex of the enzyme and the channel traffic to PIP2 domains where the enzyme makes phosphatidic acid that opens the channel.[9]
See also
- Tandem pore domain potassium channel
References
- ↑ "Mapping of human potassium channel genes TREK-1 (KCNK2) and TASK (KCNK3) to chromosomes 1q41 and 2p23". Genomics 51 (3): 478–9. Oct 1998. doi:10.1006/geno.1998.5397. PMID 9721223.
- ↑ "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacol Rev 57 (4): 527–40. Dec 2005. doi:10.1124/pr.57.4.12. PMID 16382106. https://escholarship.org/uc/item/3k15p5vt.
- ↑ 3.0 3.1 "Entrez Gene: KCNK2 potassium channel, subfamily K, member 2". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3776.
- ↑ Fink, M.; Duprat, F.; Lesage, F.; Reyes, R.; Romey, G.; Heurteaux, C.; Lazdunski, M. (1996). "Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel". The EMBO Journal 15 (24): 6854–6862. doi:10.1002/j.1460-2075.1996.tb01077.x. PMID 9003761.
- ↑ 5.0 5.1 Patel, A. J.; Honoré, E.; Maingret, F.; Lesage, F.; Fink, M.; Duprat, F.; Lazdunski, M. (1998). "A mammalian two pore domain mechano-gated S-like K+ channel". The EMBO Journal 17 (15): 4283–4290. doi:10.1093/emboj/17.15.4283. PMID 9687497.
- ↑ Giorda, R.; Weisberg, E. P.; Ip, T. K.; Trucco, M. (1992). "Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1". Journal of Immunology 149 (6): 1957–1963. doi:10.4049/jimmunol.149.6.1957. PMID 1517565.
- ↑ Patel, AJ; Lazdunski, M; Honoré, E (2001). "Lipid and mechano-gated 2P domain K(+) channels". Curr Opin Cell Biol 13 (4): 422–428. doi:10.1016/s0955-0674(00)00231-3. PMID 11454447.
- ↑ Nayebosadri, Arman; Petersen, E. Nicolas; Cabanos, Cerrone; Hansen, Scott B. (2018) (in en). A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force. Social Science Research Network. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3155650.
- ↑ Pavel, MA; Petersen, EN; Wang, H; Lerner, RA; Hansen, SB (28 May 2020). "Studies on the mechanism of general anesthesia.". Proceedings of the National Academy of Sciences of the United States of America 117 (24): 13757–13766. doi:10.1073/pnas.2004259117. PMID 32467161. Bibcode: 2020PNAS..11713757P.
Further reading
- "Potassium leak channels and the KCNK family of two-P-domain subunits.". Nat. Rev. Neurosci. 2 (3): 175–84. 2001. doi:10.1038/35058574. PMID 11256078. https://escholarship.org/uc/item/9z7112ns.
- Honoré E (2007). "The neuronal background K2P channels: focus on TREK1.". Nat. Rev. Neurosci. 8 (4): 251–61. doi:10.1038/nrn2117. PMID 17375039.
- "Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel.". EMBO J. 15 (24): 6854–62. 1997. doi:10.1002/j.1460-2075.1996.tb01077.x. PMID 9003761.
- "Inhalational anesthetics activate two-pore-domain background K+ channels.". Nat. Neurosci. 2 (5): 422–6. 1999. doi:10.1038/8084. PMID 10321245.
- "Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel.". Pflügers Arch. 439 (6): 714–22. 2000. doi:10.1007/s004240050997. PMID 10784345.
- "Beam me up, Scottie! TREK channels swing both ways.". Nat. Neurosci. 4 (5): 457–8. 2001. doi:10.1038/87402. PMID 11319549.
- "KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel.". Nat. Neurosci. 4 (5): 486–91. 2001. doi:10.1038/87434. PMID 11319556. https://escholarship.org/uc/item/4ft0c4xw.
- "An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1.". J. Biol. Chem. 277 (51): 49186–99. 2003. doi:10.1074/jbc.M207233200. PMID 12368289.
- "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M.
- "Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis.". Exp. Cell Res. 288 (1): 35–50. 2003. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
- "Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: physiological impact in acidosis and alkalosis.". Am. J. Physiol., Cell Physiol. 286 (2): C272–82. 2004. doi:10.1152/ajpcell.00334.2003. PMID 14522822.
- "Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes.". Genomics 84 (1): 205–10. 2005. doi:10.1016/j.ygeno.2004.01.011. PMID 15203218.
- "Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine.". Br. J. Pharmacol. 144 (6): 821–9. 2005. doi:10.1038/sj.bjp.0706068. PMID 15685212.
- "Structural requirements for O2 sensing by the human tandem-P domain channel, hTREK1.". Biochem. Biophys. Res. Commun. 331 (4): 1253–6. 2005. doi:10.1016/j.bbrc.2005.04.042. PMID 15883010.
- "Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels.". J. Biol. Chem. 280 (34): 30175–84. 2005. doi:10.1074/jbc.M503862200. PMID 16006563.
- "Expression of the mechanosensitive 2PK+ channel TREK-1 in human osteoblasts.". J. Cell. Physiol. 206 (3): 738–48. 2006. doi:10.1002/jcp.20536. PMID 16250016.
- "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. 2006. doi:10.1101/gr.4039406. PMID 16344560.
External links
- KCNK2+protein,+human 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.
![]() | Original source: https://en.wikipedia.org/wiki/KCNK2.
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