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KCNK2

{{Short description|Protein-coding gene in the species Homo sapiens}}

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{{Infobox_gene}}

Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the KCNK2 gene.{{cite journal | vauthors = Lesage F, Lazdunski M | title = Mapping of human potassium channel genes TREK-1 (KCNK2) and TASK (KCNK3) to chromosomes 1q41 and 2p23 | journal = Genomics | volume = 51 | issue = 3 | pages = 478–479 | date = Oct 1998 | pmid = 9721223 | doi = 10.1006/geno.1998.5397 }}{{cite journal | vauthors = Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S | title = International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels | journal = Pharmacological Reviews | volume = 57 | issue = 4 | pages = 527–540 | date = Dec 2005 | pmid = 16382106 | doi = 10.1124/pr.57.4.12 | s2cid = 7356601 | url = https://escholarship.org/uc/item/3k15p5vt }}{{cite web | title = Entrez Gene: KCNK2 potassium channel, subfamily K, member 2 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3776 }}

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.

==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.{{Cite journal | vauthors = Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, Lazdunski M | title = Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel | journal = The EMBO Journal | volume = 15 | issue = 24 | pages = 6854–6862 | year = 1996 | pmid = 9003761 | pmc = 452511 | doi = 10.1002/j.1460-2075.1996.tb01077.x }} The C-terminal of TREK-1 channels plays a role in the mechanosensitivity of the channels.{{Cite journal | vauthors = Patel AJ, Honoré E, Maingret F, Lesage F, Fink M, Duprat F, Lazdunski M | title = A mammalian two pore domain mechano-gated S-like K+ channel | journal = The EMBO Journal | volume = 17 | issue = 15 | pages = 4283–4290 | year = 1998 | pmid = 9687497 | pmc = 1170762 | doi = 10.1093/emboj/17.15.4283 }}

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.{{Cite journal | vauthors = Giorda R, Weisberg EP, Ip TK, Trucco M | title = Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1 | journal = Journal of Immunology | location = Baltimore, Md | volume = 149 | issue = 6 | pages = 1957–1963 | year = 1992 | pmid = 1517565 | doi = 10.4049/jimmunol.149.6.1957 }}

In the absence of a properly functioning cytoskeleton, TREK-1 channels can still open via mechanical gating. 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.{{cite journal | vauthors = Patel A, Lazdunski M, Honoré E | title = Lipid and mechano-gated 2P domain K(+) channels | journal = Current Opinion in Cell Biology | volume = 13 | issue = 4 | pages = 422–428 | year = 2001 | pmid = 11454447 | doi = 10.1016/s0955-0674(00)00231-3 }} The change in thickness is thought to be sensed by an amphipathic helix that extends from the inner leaflet of the membrane.{{cite journal | vauthors = Nayebosadri A, Petersen EN, Cabanos C, Hansen SB | title = A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force | date = 2018 | url = https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3155650 | publisher = Social Science Research Network | ssrn = 3155650 | language = en }}

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.{{cite journal | vauthors = Pavel M, Petersen E, Wang H, Lerner R, Hansen S | title = Studies on the mechanism of general anesthesia. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 117 | issue = 24 | pages = 13757–13766 | date = 28 May 2020 | pmid = 32467161 | pmc = 7306821 | doi = 10.1073/pnas.2004259117 | bibcode = 2020PNAS..11713757P | doi-access = free }}

See also

References

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Further reading

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  • {{cite journal | vauthors = Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N | title = Potassium leak channels and the KCNK family of two-P-domain subunits. | journal = Nature Reviews. Neuroscience | volume = 2 | issue = 3 | pages = 175–184 | year = 2001 | pmid = 11256078 | doi = 10.1038/35058574 | s2cid = 9682396 | url = https://escholarship.org/uc/item/9z7112ns }}
  • {{cite journal | vauthors = E H | title = The neuronal background K2P channels: focus on TREK1. | journal = Nature Reviews. Neuroscience | volume = 8 | issue = 4 | pages = 251–261 | year = 2007 | pmid = 17375039 | doi = 10.1038/nrn2117 | s2cid = 21421846 }}
  • {{cite journal | vauthors = Fink M, Duprat F, Lesage F, etal | title = Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. | journal = The EMBO Journal | volume = 15 | issue = 24 | pages = 6854–6862 | year = 1997 | pmid = 9003761 | pmc = 452511 | doi = 10.1002/j.1460-2075.1996.tb01077.x }}
  • {{cite journal | vauthors = Patel AJ, Honoré E, Lesage F, etal | title = Inhalational anesthetics activate two-pore-domain background K+ channels. | journal = Nature Neuroscience | volume = 2 | issue = 5 | pages = 422–426 | year = 1999 | pmid = 10321245 | doi = 10.1038/8084 | s2cid = 23092576 }}
  • {{cite journal | vauthors = Meadows HJ, Benham CD, Cairns W, etal | title = Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel. | journal = Pflugers Archiv | location = European Journal of Physiology | volume = 439 | issue = 6 | pages = 714–722 | year = 2000 | pmid = 10784345 | doi = 10.1007/s004240050997 }}
  • {{cite journal | vauthors = Maylie J, Adelman JP | title = Beam me up, Scottie! TREK channels swing both ways. | journal = Nature Neuroscience | volume = 4 | issue = 5 | pages = 457–458 | year = 2001 | pmid = 11319549 | doi = 10.1038/87402 | s2cid = 5982574 }}
  • {{cite journal | vauthors = Bockenhauer D, Zilberberg N, Goldstein SA | title = KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel. | journal = Nature Neuroscience | volume = 4 | issue = 5 | pages = 486–491 | year = 2001 | pmid = 11319556 | doi = 10.1038/87434 | s2cid = 7658182 | url = https://escholarship.org/uc/item/4ft0c4xw }}
  • {{cite journal | vauthors = Enyeart JJ, Xu L, Danthi S, Enyeart JA | title = An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1. | journal = Journal of Biological Chemistry | volume = 277 | issue = 51 | pages = 49186–49199 | year = 2003 | pmid = 12368289 | doi = 10.1074/jbc.M207233200 | doi-access = free }}
  • {{cite journal | vauthors = Strausberg RL, Feingold EA, Grouse LH, etal | title = Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16899–16903 | year = 2003 | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 | bibcode = 2002PNAS...9916899M | doi-access = free }}
  • {{cite journal | vauthors = Imabayashi H, Mori T, Gojo S, etal | title = Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrosphere formation with expression profiling by large-scale cDNA analysis. | journal = Experimental Cell Research | volume = 288 | issue = 1 | pages = 35–50 | year = 2003 | pmid = 12878157 | doi = 10.1016/S0014-4827(03)00130-7 }}
  • {{cite journal | vauthors = Miller P, Peers C, Kemp PJ | title = Polymodal regulation of hTREK1 by pH, arachidonic acid, and hypoxia: physiological impact in acidosis and alkalosis. | journal = American Journal of Physiology. Cell Physiology | volume = 286 | issue = 2 | pages = C272–82 | year = 2004 | pmid = 14522822 | doi = 10.1152/ajpcell.00334.2003 | s2cid = 25421690 }}
  • {{cite journal | vauthors = Fu GK, Wang JT, Yang J, etal | title = Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes. | journal = Genomics | volume = 84 | issue = 1 | pages = 205–210 | year = 2005 | pmid = 15203218 | doi = 10.1016/j.ygeno.2004.01.011 }}
  • {{cite journal | vauthors = Kennard LE, Chumbley JR, Ranatunga KM, etal | title = Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine. | journal = British Journal of Pharmacology | volume = 144 | issue = 6 | pages = 821–829 | year = 2005 | pmid = 15685212 | pmc = 1576064 | doi = 10.1038/sj.bjp.0706068 }}
  • {{cite journal | vauthors = Miller P, Kemp PJ, Peers C | title = Structural requirements for O2 sensing by the human tandem-P domain channel, hTREK1. | journal = Biochemical and Biophysical Research Communications | volume = 331 | issue = 4 | pages = 1253–1256 | year = 2005 | pmid = 15883010 | doi = 10.1016/j.bbrc.2005.04.042 }}
  • {{cite journal | vauthors = Murbartián J, Lei Q, Sando JJ, Bayliss DA | title = Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. | journal = Journal of Biological Chemistry | volume = 280 | issue = 34 | pages = 30175–30184 | year = 2005 | pmid = 16006563 | doi = 10.1074/jbc.M503862200 | doi-access = free }}
  • {{cite journal | vauthors = Hughes S, Magnay J, Foreman M, etal | title = Expression of the mechanosensitive 2PK+ channel TREK-1 in human osteoblasts. | journal = Journal of Cellular Physiology | volume = 206 | issue = 3 | pages = 738–748 | year = 2006 | pmid = 16250016 | doi = 10.1002/jcp.20536 | s2cid = 1788790 }}
  • {{cite journal | vauthors = Kimura K, Wakamatsu A, Suzuki Y, etal | title = Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. | journal = Genome Research | volume = 16 | issue = 1 | pages = 55–65 | year = 2006 | pmid = 16344560 | pmc = 1356129 | doi = 10.1101/gr.4039406 }}

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External links

  • {{MeshName|KCNK2+protein,+human}}

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{{Ion channels|g3}}

Category:Ion channels