Genomes and Genes
Gene Symbol: TREK 1
Description: potassium channel, subfamily K, member 2
Alias: A430027H14Rik, AI848635, TREK-1, potassium channel subfamily K member 2, TREK-1 K(+) channel subunit, outward rectifying potassium channel protein TREK-1, two pore potassium channel TPKC1
Products: TREK 1
- Blondeau N, Petrault O, Manta S, Giordanengo V, Gounon P, Bordet R, et al. Polyunsaturated fatty acids are cerebral vasodilators via the TREK-1 potassium channel. Circ Res. 2007;101:176-84 pubmed
- Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, et al. TREK-1, a K+ channel involved in polymodal pain perception. EMBO J. 2006;25:2368-76 pubmed..TREK-1 appears as an important ion channel for polymodal pain perception and as an attractive target for the development of new analgesics. ..
- Mazella J, Petrault O, Lucas G, Deval E, Béraud Dufour S, Gandin C, et al. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010;8:e1000355 pubmed publisher..Spadin can be regarded as the first natural antidepressant peptide identified. It corresponds to a new concept to address the treatment of depression. ..
- Sandoz G, Bell S, Isacoff E. Optical probing of a dynamic membrane interaction that regulates the TREK1 channel. Proc Natl Acad Sci U S A. 2011;108:2605-10 pubmed publisher..In keeping with this relation, inhibition of TREK1 current by fluoxetine is found to be accompanied by dissociation of the C-terminal domain from the membrane. ..
- Honore E, Maingret F, Lazdunski M, Patel A. An intracellular proton sensor commands lipid- and mechano-gating of the K(+) channel TREK-1. EMBO J. 2002;21:2968-76 pubmed..We conclude that protonation of E306 tunes the TREK-1 mechanical setpoint and thus sets lipid sensitivity. ..
- Fink M, Duprat F, Lesage F, Reyes R, Romey G, Heurteaux C, et al. Cloning, functional expression and brain localization of a novel unconventional outward rectifier K+ channel. EMBO J. 1996;15:6854-62 pubmed..They also show that different members in this structural family can have totally different functional properties. ..
- Sandoz G, Douguet D, Chatelain F, Lazdunski M, Lesage F. Extracellular acidification exerts opposite actions on TREK1 and TREK2 potassium channels via a single conserved histidine residue. Proc Natl Acad Sci U S A. 2009;106:14628-33 pubmed publisher..The differential sensitivity of TREK1 and TREK2 to external pH variations discriminates between these two K(+) channels that otherwise share the same regulations by physical and chemical stimuli, and by hormones and neurotransmitters. ..
- Noel J, Zimmermann K, Busserolles J, Deval E, Alloui A, Diochot S, et al. The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. EMBO J. 2009;28:1308-18 pubmed publisher..Together TREK-1 and TRAAK channels are important regulators of nociceptor activation by cold, particularly in the nociceptor population that is not activated by menthol. ..
- Murbartián J, Lei Q, Sando J, Bayliss D. Sequential phosphorylation mediates receptor- and kinase-induced inhibition of TREK-1 background potassium channels. J Biol Chem. 2005;280:30175-84 pubmed..Together, these data support a sequential phosphorylation model in which receptor-induced kinase activation drives modification at Ser-333 that enables subsequent phosphorylation at Ser-300 to inhibit TREK-1 channel activity. ..
- Heurteaux C, Lucas G, Guy N, El Yacoubi M, Thümmler S, Peng X, et al. Deletion of the background potassium channel TREK-1 results in a depression-resistant phenotype. Nat Neurosci. 2006;9:1134-41 pubmed..Our results indicate that alterations in the functioning, regulation or both of the TREK-1 channel may alter mood, and that this particular K+ channel may be a potential target for new antidepressants. ..
- Nicolas M, Lesage F, Reyes R, Barhanin J, Demêmes D. Localization of TREK-1, a two-pore-domain K+ channel in the peripheral vestibular system of mouse and rat. Brain Res. 2004;1017:46-52 pubmed..TREK-1 may subserve some neuroprotective function in afferent nerve fibers as well as play a role in endolymph potassium homeostasis. ..
- Hwang E, Kim E, Yarishkin O, Woo D, Han K, Park N, et al. A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat Commun. 2014;5:3227 pubmed publisher..TWIK-1/TREK-1 heterodimers mediate astrocytic passive conductance and cannabinoid-induced glutamate release from astrocytes. Our study sheds new light on the diversity of K2P channels. ..
- Maksaev G, Milac A, Anishkin A, Guy H, Sukharev S. Analyses of gating thermodynamics and effects of deletions in the mechanosensitive channel TREK-1: comparisons with structural models. Channels (Austin). 2011;5:34-42 pubmed..C219A did not compromise channel activity, whereas the C159A/S mutants were essentially inactive. Treatment with ?-mercaptoethanol suggested that none of these cysteines form functionally-important disulfides. ..
- Monaghan K, Baker S, Dwyer L, Hatton W, Sik Park K, Sanders K, et al. The stretch-dependent potassium channel TREK-1 and its function in murine myometrium. J Physiol. 2011;589:1221-33 pubmed publisher..Up-regulation of these channels stabilizes membrane potential and controls contraction during pregnancy and down-regulation of these channels induces the onset of delivery. ..
- Schwingshackl A, Lopez B, Teng B, Luellen C, Lesage F, Belperio J, et al. Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins. Am J Physiol Lung Cell Mol Physiol. 2017;313:L1030-L1046 pubmed publisher..1/thyroid transcription factor-1 (TTF-1) or c-jun, or lamellar body levels. Prophylactic Curosurf administration did not improve lung injury scores or compliance in triple KO mice. ..
- Woo D, Han K, Shim J, Yoon B, Kim E, Bae J, et al. TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell. 2012;151:25-40 pubmed publisher..Our results reveal two distinct sources of astrocytic glutamate that can differentially influence neighboring neurons. ..
- Namiranian K, Lloyd E, Crossland R, Marrelli S, Taffet G, Reddy A, et al. Cerebrovascular responses in mice deficient in the potassium channel, TREK-1. Am J Physiol Regul Integr Comp Physiol. 2010;299:R461-9 pubmed publisher..There was no sign of TREK-1-like currents in CVSMCs from WT mice, and there were no major differences in currents between the genotypes. We conclude that regulation of arterial diameter is not altered in mice lacking TREK-1. ..
- Bagriantsev S, Clark K, Minor D. Metabolic and thermal stimuli control K(2P)2.1 (TREK-1) through modular sensory and gating domains. EMBO J. 2012;31:3297-308 pubmed publisher..This marked distinction between gating and sensory elements suggests a general design principle that may underlie the function of a variety of temperature-sensitive channels. ..
- Hao J, Padilla F, Dandonneau M, Lavebratt C, Lesage F, Noel J, et al. Kv1.1 channels act as mechanical brake in the senses of touch and pain. Neuron. 2013;77:899-914 pubmed publisher..By balancing the activity of excitatory mechanotransducers, Kv1.1 acts as a mechanosensitive brake that regulates mechanical sensitivity of fibers associated with mechanical perception. ..
- Berrier C, Pozza A, de Lacroix de Lavalette A, Chardonnet S, Mesneau A, Jaxel C, et al. The purified mechanosensitive channel TREK-1 is directly sensitive to membrane tension. J Biol Chem. 2013;288:27307-14 pubmed publisher..These results indicate that TREK-1 is directly sensitive to membrane tension. ..
- Bittner S, Ruck T, Schuhmann M, Herrmann A, Moha Ou Maati H, Bobak N, et al. Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat Med. 2013;19:1161-5 pubmed publisher..These beneficial effects were reduced in Kcnk2(-/-) mice, suggesting TREK-1 activating compounds may be used therapeutically to treat diseases related to BBB dysfunction. ..
- Hund T, Snyder J, Wu X, Glynn P, Koval O, Onal B, et al. ?(IV)-Spectrin regulates TREK-1 membrane targeting in the heart. Cardiovasc Res. 2014;102:166-75 pubmed publisher..These data provide new insight into membrane targeting of TREK-1 in the heart and establish a broader role for ?(IV)-spectrin in organizing functional membrane domains critical for normal heart function. ..
- Bittner S, Ruck T, Fernandez Orth J, Meuth S. TREK-king the blood-brain-barrier. J Neuroimmune Pharmacol. 2014;9:293-301 pubmed publisher..Here we summarize these findings and discuss the implications in diseases related to BBB dysfunction. ..
- Lengyel M, Czirják G, Enyedi P. Formation of Functional Heterodimers by TREK-1 and TREK-2 Two-pore Domain Potassium Channel Subunits. J Biol Chem. 2016;291:13649-61 pubmed publisher..Formation of TREK-1/TREK-2 channels was also demonstrated in native dorsal root ganglion neurons indicating that heterodimerization may provide greater diversity of leak K(+) conductances also in native tissues. ..
- Devilliers M, Busserolles J, Lolignier S, Deval E, Pereira V, Alloui A, et al. Activation of TREK-1 by morphine results in analgesia without adverse side effects. Nat Commun. 2013;4:2941 pubmed publisher..These observations suggest that direct activation of the TREK-1 K(+) channel, acting downstream from the ? opioid receptor, might have strong analgesic effects without opioid-like adverse effects. ..
- Dey D, Eckle V, Vitko I, Sullivan K, Lasiecka Z, Winckler B, et al. A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus. Epilepsia. 2014;55:203-13 pubmed publisher..This study paves the way for an alternative gene therapy treatment of status epilepticus, and provides the rationale for studies of AAV-TREK-M's effect on spontaneous seizures in chronic models of temporal lobe epilepsy. ..
- Stebe S, Schellig K, Lesage F, Breer H, Fleischer J. The thermosensitive potassium channel TREK-1 contributes to coolness-evoked responses of Grueneberg ganglion neurons. Cell Mol Neurobiol. 2014;34:113-22 pubmed publisher..Moreover, the present findings provide the first evidence of how thermosensory GG neurons are activated by given temperature stimuli in the absence of thermo-TRPs. ..
- Meadows H, Benham C, Cairns W, Gloger I, Jennings C, Medhurst A, et al. Cloning, localisation and functional expression of the human orthologue of the TREK-1 potassium channel. Pflugers Arch. 2000;439:714-22 pubmed..Only low levels of expression were seen in the majority of peripheral regions. Thus, hTREK-1, although functionally and pharmacologically similar to mouse TREK-1, appears to have a more CNS-specific distribution. ..
- Lee A, Tse F, Tse A. Arginine Vasopressin Potentiates the Stimulatory Action of CRH on Pituitary Corticotropes via a Protein Kinase C-Dependent Reduction of the Background TREK-1 Current. Endocrinology. 2015;156:3661-72 pubmed publisher..We suggest that this mechanism contributes to the potentiating action of AVP on CRH-evoked ACTH secretion. ..
- Blin S, Ben Soussia I, Kim E, Brau F, Kang D, Lesage F, et al. Mixing and matching TREK/TRAAK subunits generate heterodimeric K2P channels with unique properties. Proc Natl Acad Sci U S A. 2016;113:4200-5 pubmed publisher..These results unveil a previously unexpected diversity of K2P channels that will be challenging to analyze in vivo, but which opens new perspectives for the development of clinically relevant drugs. ..
- Froese A, Breher S, Waldeyer C, Schindler R, Nikolaev V, Rinné S, et al. Popeye domain containing proteins are essential for stress-mediated modulation of cardiac pacemaking in mice. J Clin Invest. 2012;122:1119-30 pubmed publisher..Mice with mutant Popdc1 and Popdc2 alleles are therefore useful models for the dissection of the mechanisms causing pacemaker dysfunction and could aid in the development of strategies for therapeutic intervention. ..
- Nishihara E, Tsaih S, Tsukahara C, Langley S, Sheehan S, DiPetrillo K, et al. Quantitative trait loci associated with blood pressure of metabolic syndrome in the progeny of NZO/HILtJxC3H/HeJ intercrosses. Mamm Genome. 2007;18:573-83 pubmed..These results enhance our understanding of complicated genetic factors of hypertension in metabolic diseases. ..
- Ford K, Arroyo D, Kay J, Lloyd E, Bryan R, Sanes J, et al. A role for TREK1 in generating the slow afterhyperpolarization in developing starburst amacrine cells. J Neurophysiol. 2013;109:2250-9 pubmed publisher..Our model offers a novel pathway for the activation of a conductance that is physiologically important. ..
- Schwingshackl A, Teng B, Ghosh M, Lim K, Tigyi G, Narayanan D, et al. Regulation of interleukin-6 secretion by the two-pore-domain potassium channel Trek-1 in alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2013;304:L276-86 pubmed publisher..The results of this study identify Trek-1 as a new potential target for the development of novel treatment strategies against acute lung injury. ..
- Naik A, Kulkarni S, Lewis K, Taatjes D, Jena B. Functional Reconstitution of the Insulin-Secreting Porosome Complex in Live Cells. Endocrinology. 2016;157:54-60 pubmed publisher..These results, establish a new paradigm in porosome-mediated insulin secretion in Î²-cells. ..
- Dominguez Lopez S, Howell R, Gobbi G. Characterization of serotonin neurotransmission in knockout mice: implications for major depression. Rev Neurosci. 2012;23:429-43 pubmed publisher..The correlation of 5-HT activity and behavior could be a predictor factor for understanding the role of receptors, channels and enzymes in depression, and could be used also to assess the potential antidepressive effects of novel drugs. ..
- Mirkovic K, Palmersheim J, Lesage F, Wickman K. Behavioral characterization of mice lacking Trek channels. Front Behav Neurosci. 2012;6:60 pubmed publisher..Collectively, these data argue that despite their broad distribution in the CNS, Trek channels exert a minimal influence on a wide-range of behaviors. ..
- Hur C, Kim E, Cho S, Cho Y, Yoon S, Tak H, et al. K(+) efflux through two-pore domain K(+) channels is required for mouse embryonic development. Reproduction. 2012;143:625-36 pubmed publisher..The blockade of K(2P) channels acidified the intracellular pH and depolarized the membrane potential. These results suggest that K(2P) channels could improve mouse embryonic development through the modulation of gating by activators. ..
- Bockenhauer D, Nimmakayalu M, Ward D, Goldstein S, Gallagher P. Genomic organization and chromosomal localization of the murine 2 P domain potassium channel gene Kcnk8: conservation of gene structure in 2 P domain potassium channels. Gene. 2000;261:365-72 pubmed
- Azzalin A, Ferrara V, Arias A, Cerri S, Avella D, Pisu M, et al. Interaction between the cellular prion (PrPC) and the 2P domain K+ channel TREK-1 protein. Biochem Biophys Res Commun. 2006;346:108-15 pubmed..Our results indicated a novel PrP(C) interacting protein and suggested that this complex might be relevant in modulating a variety of electrophysiological-dependent cellular responses. ..
- Bando Y, Hirano T, Tagawa Y. Dysfunction of KCNK potassium channels impairs neuronal migration in the developing mouse cerebral cortex. Cereb Cortex. 2014;24:1017-29 pubmed publisher..Taken together, our results suggest that dysfunction of KCNK9 causes a migration defect in the cortex via an activity-dependent mechanism. ..
- Peyronnet R, Sharif Naeini R, Folgering J, Arhatte M, Jodar M, El Boustany C, et al. Mechanoprotection by polycystins against apoptosis is mediated through the opening of stretch-activated K(2P) channels. Cell Rep. 2012;1:241-50 pubmed publisher..We propose that this mechanism is at play in other important pathologies associated with apoptosis and in which pressure or flow stimulation is altered, including heart failure or atherosclerosis. ..
- Benesova J, Rusnakova V, Honsa P, Pivonkova H, Dzamba D, Kubista M, et al. Distinct expression/function of potassium and chloride channels contributes to the diverse volume regulation in cortical astrocytes of GFAP/EGFP mice. PLoS ONE. 2012;7:e29725 pubmed publisher..Thus, we propose that the diverse volume changes displayed by cortical astrocytes during OGD mainly result from their distinct expression patterns of ClC2 and K(2P) channels. ..
- Lolicato M, Arrigoni C, Mori T, Sekioka Y, Bryant C, Clark K, et al. K2P2.1 (TREK-1)-activator complexes reveal a cryptic selectivity filter binding site. Nature. 2017;547:364-368 pubmed publisher..Together, our data reveal a druggable K2P site that stabilizes the C-type gate 'leak mode' and provide direct evidence for K2P selectivity filter gating. ..
- Chemin J, Patel A, Duprat F, Zanzouri M, Lazdunski M, Honore E. Lysophosphatidic acid-operated K+ channels. J Biol Chem. 2005;280:4415-21 pubmed..Gating conversion of the 2P domain K+ channels by intracellular LPA represents a novel form of ion channel regulation. Thus, the TREK and TRAAK channels should be included in the LPA-associated physiological and disease states. ..
- Fang Y, Huang X, Wan Y, Tian H, Tian Y, Wang W, et al. Deficiency of TREK-1 potassium channel exacerbates secondary injury following spinal cord injury in mice. J Neurochem. 2017;141:236-246 pubmed publisher..In summary, our findings provide the first in vivo evidence suggesting that TREK-1 may thereby constitute a promising therapeutic target to treat acute SCI. ..
- Veale E, Rees K, Mathie A, Trapp S. Dominant negative effects of a non-conducting TREK1 splice variant expressed in brain. J Biol Chem. 2010;285:29295-304 pubmed publisher..These results indicate that the N-terminal domain and first transmembrane domain of TREK1 are likely to be important for channel dimerization and trafficking to the plasma membrane. ..
- Vallee N, Rostain J, Risso J. Low susceptibility to inert gases and pressure symptoms in TREK-1-deficient mice. Neuroreport. 2009;20:343-7 pubmed..TREK-1 channels seem to play a key role in modulating the anaesthetic potential of inert gases and in neuroprotection...
- Unudurthi S, Wu X, Qian L, Amari F, Onal B, Li N, et al. Two-Pore K+ Channel TREK-1 Regulates Sinoatrial Node Membrane Excitability. J Am Heart Assoc. 2016;5:e002865 pubmed publisher..These findings identify a TREK-1-dependent pathway essential for normal sinoatrial node cell excitability that serves as a potential target for selectively regulating sinoatrial node cell function. ..
- La J, Schwartz E, Gebhart G. Differences in the expression of transient receptor potential channel V1, transient receptor potential channel A1 and mechanosensitive two pore-domain K+ channels between the lumbar splanchnic and pelvic nerve innervations of mouse urinary bladder an. Neuroscience. 2011;186:179-87 pubmed publisher..This study further documents heterogeneity of visceral afferents based on combinations of the five channels examined. ..
- Schindler R, Scotton C, Zhang J, Passarelli C, Ortiz Bonnin B, Simrick S, et al. POPDC1(S201F) causes muscular dystrophy and arrhythmia by affecting protein trafficking. J Clin Invest. 2016;126:239-53 pubmed publisher..Our study therefore identifies POPDC1 as a disease gene causing a very rare autosomal recessive cardiac arrhythmia and LGMD, expanding the genetic causes of this heterogeneous group of inherited rare diseases. ..
- Huang H, Liu J, Yu Y, Mo L, Ge R, Zhang H, et al. Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrier function. Cell Mol Immunol. 2016;13:110-8 pubmed publisher..Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment. ..
- Vallee N, Meckler C, Risso J, Blatteau J. Neuroprotective role of the TREK-1 channel in decompression sickness. J Appl Physiol (1985). 2012;112:1191-6 pubmed publisher..0% failed a grip test, and 31.8% died. Mice that did not express TREK-1 had lower DCS resistance and were more likely to develop neurological symptoms. We conclude that the TREK-1 potassium channel was neuroprotective for DCS. ..
- Westphalen R, Krivitski M, Amarosa A, Guy N, Hemmings H. Reduced inhibition of cortical glutamate and GABA release by halothane in mice lacking the K+ channel, TREK-1. Br J Pharmacol. 2007;152:939-45 pubmed
- Honore E, Patel A, Chemin J, Suchyna T, Sachs F. Desensitization of mechano-gated K2P channels. Proc Natl Acad Sci U S A. 2006;103:6859-64 pubmed..Desensitization and its regulation by chemical messengers is predicted to condition the physiological role of K2P channels. ..
- Koh S, Monaghan K, Sergeant G, Ro S, Walker R, Sanders K, et al. TREK-1 regulation by nitric oxide and cGMP-dependent protein kinase. An essential role in smooth muscle inhibitory neurotransmission. J Biol Chem. 2001;276:44338-46 pubmed..TREK-1 encodes a component of the stretch-activated K(+) conductance in smooth muscles and may contribute to nitrergic inhibition of gastrointestinal muscles. ..
- Kim D, Fujita A, Horio Y, Kurachi Y. Cloning and functional expression of a novel cardiac two-pore background K+ channel (cTBAK-1). Circ Res. 1998;82:513-8 pubmed..Thus, the current flowing through the channel may contribute to the cardiac cellular electrical activity as a linear background K+ conductance. Therefore, we designated the clone cTBAK (cardiac two-pore background K+ channel). ..
- Lembrechts R, Pintelon I, Schnorbusch K, Timmermans J, Adriaensen D, Brouns I. Expression of mechanogated two-pore domain potassium channels in mouse lungs: special reference to mechanosensory airway receptors. Histochem Cell Biol. 2011;136:371-85 pubmed publisher..TRAAK appears to be strongly involved in regulating airway mechanosensing since it was found to be expressed on the terminals of all subpopulations of potential vagal mechanosensors. ..