Potassium channel subfamily K member 2 is a protein that in humans is encoded by the KCNK2gene.
This gene encodes K2P2.1, one of the members of the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that leaks potassium out of the cell to control resting membrane potential. The channel can be opened, however, by certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene.
Another name for this channel is TREK-1. 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. The C-terminal of TREK-1 channels plays a role in the mechanosensitivity of the channels.
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.
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. The insertion of certain compounds into the membrane is thought to mediate the opening of TREK-1 by forming a curve in the membrane.
^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. PMID9721223. doi:10.1006/geno.1998.5397.
^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. PMID16382106. doi:10.1124/pr.57.4.12.
^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 (Baltimore, Md. : 1950). 149 (6): 1957–1963. PMID1517565.
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. PMID11256078. doi:10.1038/35058574.
Meadows HJ, Benham CD, Cairns W, et al. (2000). "Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel.". Pflugers Arch. 439 (6): 714–22. PMID10784345. doi:10.1007/s004240050997.
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. PMID11319556. doi:10.1038/87434.
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. PMID12368289. doi:10.1074/jbc.M207233200.
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. PMID12878157. doi:10.1016/S0014-4827(03)00130-7.
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. PMID14522822. doi:10.1152/ajpcell.00334.2003.
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. PMID15203218. doi:10.1016/j.ygeno.2004.01.011.
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. PMID15883010. doi:10.1016/j.bbrc.2005.04.042.
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. PMID16006563. doi:10.1074/jbc.M503862200.
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. PMID16250016. doi:10.1002/jcp.20536.