K<sub>2P</sub>10.1 | Two P domain potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

K2P10.1

Target id: 521

Nomenclature: K2P10.1

Family: Two P domain potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for K2P10.1 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 2 538 14q31 KCNK10 potassium two pore domain channel subfamily K member 10 1
Mouse 4 2 535 12 E Kcnk10 potassium channel, subfamily K, member 10
Rat 4 2 538 6q32 Kcnk10 potassium two pore domain channel subfamily K member 10
Previous and Unofficial Names
TREK-2 | potassium channel, two pore domain subfamily K, member 10 | potassium channel
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human two pore domain potassium ion channel TREK2 (K2P10.1) in complex with norfluoxetine
PDB Id:  4XDK
Ligand:  norfluoxetine
Resolution:  3.6Å
Species:  Human
References:  3
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Not determined
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
PLD2 2
AKAP150 11
Mtap2 10
Associated Protein Comments
Heteromultimers shown to form in vivo: K2P10 has been reported to form a heterodimer with K2P1 in heterologous expression systems, however the in vivo formation of this heterodimer and its function remain unknown [6].

Protein-protein interactions: K2P10 has been reported to respond to numerous proteins, including:

AKAP150: The A-kinase-anchoring protein AKAP150 binds to the C-terminus of K2P10, increasing the kinetic of channel inactivation by Gs coupled receptors and decreasing inhibition by Gq coupled receptors [11].
Mtap2: The microtubule associated protein 2 Mtap2 binds to the C-terminus of K2P10 to increase channel density at the plasma membrane [10].
PLD2: PLD2, a phosphatidic acid (PA) producing enzyme, binds to the C-terminus of K2P10 to potentiate channel activity in a PA-dependent manner [2].
Functional Characteristics
Background current

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Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
docosahexaenoic acid Hs - - - - - 9
[9]
linoleic acid Hs - - - - - 9
[9]
arachidonic acid Hs - - - - - 9
studied at 1-10 µM [9]
halothane Hs - - - - - 9
studied at 1-5 mM [9]
lysophosphatidylcholine Hs - - - - - 9
[9]
Activator Comments
A concentration of 0.5 mM halothane maximally activates the channel by 2.6-fold [9]. The channel is also activated by the neuroprotective drug riluzole. Channel activity is stimulated by 8.4 times by arachidonic acid, and 5.1 times by lysophosphatidylinositol [9].
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
quinidine Rn - - - - - 5
[5]
Tissue Distribution
Kidney, pancreas, thymus, liver, heart.
Species:  Human
Technique:  RT-PCR
References:  4
Biologically Significant Variant Comments
Three alternate splice forms of K2P10 have been identified [4,9]. To date, the pharmacological and physiological significance of the variant isoforms remains unknown.
General Comments
‘Activation’ and ‘deactivation’ with voltage steps appear to be instantaneous. Splice variants have been identified in human and rat. The rat variant is reported to have a conductance of 68pS and to be expressed in brain. K2P10 like currents are observed in cerebellar granular neurons, magnocellular neurosecretory cells of rat supraoptic nucleus [5,8] and rat cortical astrocytes [7].

References

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1. Bang H, Kim Y, Kim D. (2000) TREK-2, a new member of the mechanosensitive tandem-pore K+ channel family. J. Biol. Chem., 275 (23): 17412-9. [PMID:10747911]

2. Comoglio Y, Levitz J, Kienzler MA, Lesage F, Isacoff EY, Sandoz G. (2014) Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid. Proc. Natl. Acad. Sci. U.S.A., 111 (37): 13547-52. [PMID:25197053]

3. Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S et al.. (2015) K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac. Science, 347 (6227): 1256-9. [PMID:25766236]

4. Gu W, Schlichthörl G, Hirsch JR, Engels H, Karschin C, Karschin A, Derst C, Steinlein OK, Daut J. (2002) Expression pattern and functional characteristics of two novel splice variants of the two-pore-domain potassium channel TREK-2. J. Physiol. (Lond.), 539 (Pt 3): 657-68. [PMID:11897838]

5. Han J, Truell J, Gnatenco C, Kim D. (2002) Characterization of four types of background potassium channels in rat cerebellar granule neurons. J. Physiol. (Lond.), 542 (Pt 2): 431-44. [PMID:12122143]

6. Hwang EM, Kim E, Yarishkin O, Woo DH, Han KS, Park N, Bae Y, Woo J, Kim D, Park M et al.. (2014) A disulphide-linked heterodimer of TWIK-1 and TREK-1 mediates passive conductance in astrocytes. Nat Commun, 5: 3227. [PMID:24496152]

7. Kang D, Choe C, Kim D. (2004) Functional expression of TREK-2 in insulin-secreting MIN6 cells. Biochem. Biophys. Res. Commun., 323 (1): 323-31. [PMID:15351740]

8. Kang D, Choe C, Kim D. (2005) Thermosensitivity of the two-pore domain K+ channels TREK-2 and TRAAK. J. Physiol. (Lond.), 564 (Pt 1): 103-16. [PMID:15677687]

9. Lesage F, Terrenoire C, Romey G, Lazdunski M. (2000) Human TREK2, a 2P domain mechano-sensitive K+ channel with multiple regulations by polyunsaturated fatty acids, lysophospholipids, and Gs, Gi, and Gq protein-coupled receptors. J. Biol. Chem., 275 (37): 28398-405. [PMID:10880510]

10. Sandoz G, Tardy MP, Thümmler S, Feliciangeli S, Lazdunski M, Lesage F. (2008) Mtap2 is a constituent of the protein network that regulates twik-related K+ channel expression and trafficking. J. Neurosci., 28 (34): 8545-52. [PMID:18716213]

11. Sandoz G, Thümmler S, Duprat F, Feliciangeli S, Vinh J, Escoubas P, Guy N, Lazdunski M, Lesage F. (2006) AKAP150, a switch to convert mechano-, pH- and arachidonic acid-sensitive TREK K(+) channels into open leak channels. EMBO J., 25 (24): 5864-72. [PMID:17110924]

Contributors

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How to cite this page

Leigh D. Plant, Douglas A. Bayliss, Daniel L. Minor, Jr., Gábor Czirják, Péter Enyedi, Florian Lesage, Francisco Sepúlveda, Steve A.N. Goldstein.
Two P domain potassium channels: K2P10.1. Last modified on 27/09/2017. Accessed on 16/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=521.