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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.⁵ The C-terminal of TREK-1 channels plays a role in the mechanosensitivity of the channels.⁶

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.⁷

In the absence of a properly functioning cytoskeleton, TREK-1 channels can still open via mechanical gating.⁸ 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.⁹ The change in thickness is thought to be sensed by an amphipathic helix that extends from the inner leaflet of the membrane.¹⁰

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.¹¹

See also

• Tandem pore domain potassium channel

Further reading

• Goldstein SA, Bockenhauer D, O'Kelly I, Zilberberg N (2001). "Potassium leak channels and the KCNK family of two-P-domain subunits". Nat. Rev. Neurosci. 2 (3): 175–84. doi:10.1038/35058574. PMID 11256078. S2CID 9682396.
• Honoré E (2007). "The neuronal background K2P channels: focus on TREK1". Nat. Rev. Neurosci. 8 (4): 251–61. doi:10.1038/nrn2117. PMID 17375039. S2CID 21421846.
• Fink M, Duprat F, Lesage F, et al. (1997). "Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel". EMBO J. 15 (24): 6854–62. doi:10.1002/j.1460-2075.1996.tb01077.x. PMC 452511. PMID 9003761.
• Patel AJ, Honoré E, Lesage F, et al. (1999). "Inhalational anesthetics activate two-pore-domain background K+ channels". Nat. Neurosci. 2 (5): 422–6. doi:10.1038/8084. PMID 10321245. S2CID 23092576.
• Meadows HJ, Benham CD, Cairns W, et al. (2000). "Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel". Pflügers Arch. 439 (6): 714–22. doi:10.1007/s004240050997. PMID 10784345.
• Maylie J, Adelman JP (2001). "Beam me up, Scottie! TREK channels swing both ways". Nat. Neurosci. 4 (5): 457–8. doi:10.1038/87402. PMID 11319549. S2CID 5982574.
• Bockenhauer D, Zilberberg N, Goldstein SA (2001). "KCNK2: reversible conversion of a hippocampal potassium leak into a voltage-dependent channel". Nat. Neurosci. 4 (5): 486–91. doi:10.1038/87434. PMID 11319556. S2CID 7658182.
• Enyeart JJ, Xu L, Danthi S, Enyeart JA (2003). "An ACTH- and ATP-regulated background K+ channel in adrenocortical cells is TREK-1". J. Biol. Chem. 277 (51): 49186–99. doi:10.1074/jbc.M207233200. PMID 12368289.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Imabayashi H, Mori T, Gojo S, et al. (2003). "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. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157.
• Miller P, Peers C, Kemp PJ (2004). "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. doi:10.1152/ajpcell.00334.2003. PMID 14522822. S2CID 25421690.
• Fu GK, Wang JT, Yang J, et al. (2005). "Circular rapid amplification of cDNA ends for high-throughput extension cloning of partial genes". Genomics. 84 (1): 205–10. doi:10.1016/j.ygeno.2004.01.011. PMID 15203218.
• Kennard LE, Chumbley JR, Ranatunga KM, et al. (2005). "Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine". Br. J. Pharmacol. 144 (6): 821–9. doi:10.1038/sj.bjp.0706068. PMC 1576064. PMID 15685212.
• Miller P, Kemp PJ, Peers C (2005). "Structural requirements for O2 sensing by the human tandem-P domain channel, hTREK1". Biochem. Biophys. Res. Commun. 331 (4): 1253–6. doi:10.1016/j.bbrc.2005.04.042. PMID 15883010.
• Murbartián J, Lei Q, Sando JJ, Bayliss DA (2005). "Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels". J. Biol. Chem. 280 (34): 30175–84. doi:10.1074/jbc.M503862200. PMID 16006563.
• Hughes S, Magnay J, Foreman M, et al. (2006). "Expression of the mechanosensitive 2PK+ channel TREK-1 in human osteoblasts". J. Cell. Physiol. 206 (3): 738–48. doi:10.1002/jcp.20536. PMID 16250016. S2CID 1788790.
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.

External links

• KCNK2+protein,+human at the U.S. 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.

References

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10. 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) https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3155650 ↩

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