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KCNK2

KCNK2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesKCNK2, K2p2.1, TPKC1, TREK, TREK-1, TREK1, hTREK-1c, hTREK-1e, potassium two pore domain channel subfamily K member 2
External IDsOMIM: 603219; MGI: 109366; HomoloGene: 7794; GeneCards: KCNK2; OMA:KCNK2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

3776

16526

Ensembl

ENSG00000082482

ENSMUSG00000037624

UniProt

O95069

P97438

RefSeq (mRNA)

NM_001017424
NM_001017425
NM_014217

NM_001159850
NM_001281847
NM_001281848
NM_010607
NM_001357119

RefSeq (protein)

NP_001017424
NP_001017425
NP_055032

Location (UCSC)Chr 1: 215.01 – 215.24 MbChr 1: 188.94 – 189.13 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the KCNK2 gene.[5][6][7]

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.[7]

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.[8] The C-terminal of TREK-1 channels plays a role in the mechanosensitivity of the channels.[9]

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.[10]

In the absence of a properly functioning cytoskeleton, TREK-1 channels can still open via mechanical gating.[9] 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.[11] The change in thickness is thought to be sensed by an amphipathic helix that extends from the inner leaflet of the membrane.[12]

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.[13]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000082482 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000037624 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Lesage F, Lazdunski M (Oct 1998). "Mapping of human potassium channel genes TREK-1 (KCNK2) and TASK (KCNK3) to chromosomes 1q41 and 2p23". Genomics. 51 (3): 478–9. doi:10.1006/geno.1998.5397. PMID 9721223.
  6. ^ Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (Dec 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacol Rev. 57 (4): 527–40. doi:10.1124/pr.57.4.12. PMID 16382106. S2CID 7356601.
  7. ^ a b "Entrez Gene: KCNK2 potassium channel, subfamily K, member 2".
  8. ^ 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. PMC 452511. PMID 9003761.
  9. ^ a b Patel AJ, 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. PMC 1170762. PMID 9687497.
  10. ^ Giorda R, Weisberg EP, Ip TK, 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.
  11. ^ 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.
  12. ^ Nayebosadri A, Petersen EN, Cabanos C, Hansen SB (2018). "A Membrane Thickness Sensor in TREK-1 Channels Transduces Mechanical Force". Social Science Research Network. SSRN 3155650. {{cite journal}}: Cite journal requires |journal= (help)
  13. ^ 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. Bibcode:2020PNAS..11713757P. doi:10.1073/pnas.2004259117. PMC 7306821. PMID 32467161.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Quelle: https://en.wikipedia.org/wiki/KCNK2