KCNK13

KCNK13
Identifiers
AliasesKCNK13, K2p13.1, THIK-1, THIK1, potassium two pore domain channel subfamily K member 13
External IDsOMIM: 607367; MGI: 2384976; HomoloGene: 69351; GeneCards: KCNK13; OMA:KCNK13 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

56659

217826

Ensembl

ENSG00000152315

ENSMUSG00000045404

UniProt

Q9HB14

Q8R1P5

RefSeq (mRNA)

NM_022054

NM_001164426
NM_001164427
NM_146037

RefSeq (protein)

NP_071337

NP_001157898
NP_001157899
NP_666149

Location (UCSC)Chr 14: 90.06 – 90.19 MbChr 12: 99.93 – 100.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Potassium channel, subfamily K, member 13 (KCNK13), also known as K2P13.1 or THIK-1, is a protein that in humans is encoded by the KCNK13 gene. It is a potassium channel containing two pore-forming P domains.[5][6]

Function

Ribbon structure of homodimeric two-pore potassium channel K2P13 (THIK-1). Subunits are colored in gray and purple. Transmembrane helices M1-M4, pore helix PH2 (PH1 not shown), and cap helices CH1-CH2 are labeled. Horizontal black lines represent the cell membrane, with extracellular and intracellular regions labeled.
Ribbon structure of homodimeric two-pore potassium channel K2P13 (THIK-1).[7]

K2P13.1 was first discovered in 2000 from a rat cDNA library, along with the closely related protein K2P12.1[5] The two channels were named tandem pore domain halothane-inhibited K+ channel 1 and 2 (THIK-1 and THIK-2) because the anesthetic halothane inhibited the potassium current. THIK-1 was also shown to be activated by arachidonic acid and displayed mild voltage dependence, with moderate outward rectification at low external K+ and weak inward rectification with nearly symmetrical K+ concentrations.[5][8] Later research showed that THIK-1 can be activated by G-protein-coupled receptor pathways[9] and by polyanionic lipids such as PIP2 and oleoyl-CoA.[10]

In humans, THIK-1 expression is almost exclusively restricted to microglia, where it functions as the main potassium channel and is responsible for maintaining their resting membrane potential through tonic background potassium conductance.[11] THIK-1 activity can regulate microglial ramification, surveillance, NLRP3 inflammasome activation, and subsequent release of pro-inflammatory cytokine interleukin-1β (IL-1β).[12][13][14] It also plays a role in cell shrinkage during apoptosis via caspase-8 cleavage.[15]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000152315 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045404 – 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. ^ a b c Rajan S, Wischmeyer E, Karschin C, Preisig-Müller R, Grzeschik KH, Daut J, et al. (March 2001). "THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels". The Journal of Biological Chemistry. 276 (10): 7302–7311. doi:10.1074/jbc.M008985200. PMID 11060316.
  6. ^ Goldstein SA, Bayliss DA, Kim D, Lesage F, Plant LD, Rajan S (December 2005). "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews. 57 (4): 527–540. doi:10.1124/pr.57.4.12. PMID 16382106. S2CID 7356601.
  7. ^ Rödström KE, Eymsh B, Proks P, Hayre MS, Madry C, Rowland A, et al. (2024-06-27). "CryoEM Structure of the human THIK-1 K2P K+ Channel Reveals a Lower 'Y-gate' Regulated by Lipids and Anaesthetics". bioRxiv 10.1101/2024.06.26.600475.
  8. ^ Aggarwal P, Singh S, Ravichandiran V (2021-08-01). "Two-Pore Domain Potassium Channel in Neurological Disorders". The Journal of Membrane Biology. 254 (4): 367–380. doi:10.1007/s00232-021-00189-8. ISSN 1432-1424. PMID 34169340.
  9. ^ Tateyama M, Kubo Y (2023-04-26). "Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors". PLOS ONE. 18 (4) e0284962. Bibcode:2023PLoSO..1884962T. doi:10.1371/journal.pone.0284962. ISSN 1932-6203. PMC 10132538. PMID 37099539.
  10. ^ Riel EB, Jurs BC, Cordeiro S, Musinszki M, Schewe M, Baukrowitz T (2022-02-07). "The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism". The Journal of General Physiology. 154 (2) e202112989. doi:10.1085/jgp.202112989. ISSN 0022-1295. PMC 8693234. PMID 34928298.
  11. ^ Rifat A, Ossola B, Burli RW, Dawson LA, Brice NL, Rowland A, et al. (2024-02-26). "Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia". Journal of Neuroinflammation. 21 (1) 58. doi:10.1186/s12974-024-03042-6. ISSN 1742-2094. PMC 10895799. PMID 38409076.
  12. ^ Madry C, Kyrargyri V, Arancibia-Carcamo IL, Jolivet R, Kohsaka S, Bryan RM, et al. (January 2018). "Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1". Neuron. 97 (2): 299–312.e6. doi:10.1016/j.neuron.2017.12.002. PMC 5783715. PMID 29290552.
  13. ^ Xu Z, Chen ZM, Wu X, Zhang L, Cao Y, Zhou P (2020-12-07). "Distinct Molecular Mechanisms Underlying Potassium Efflux for NLRP3 Inflammasome Activation". Frontiers in Immunology. 11 609441. doi:10.3389/fimmu.2020.609441. ISSN 1664-3224. PMC 7793832. PMID 33424864.
  14. ^ Drinkall S, Lawrence CB, Ossola B, Russell S, Bender C, Brice NB, et al. (2022). "The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation". Glia. 70 (7): 1301–1316. doi:10.1002/glia.24174. ISSN 1098-1136. PMC 9314991. PMID 35353387.
  15. ^ Sakamaki K, Ishii TM, Sakata T, Takemoto K, Takagi C, Takeuchi A, et al. (2016-11-01). "Dysregulation of a potassium channel, THIK-1, targeted by caspase-8 accelerates cell shrinkage". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1863 (11): 2766–2783. doi:10.1016/j.bbamcr.2016.08.010. ISSN 0167-4889. PMID 27566292.

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