Biology:KCNK13

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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.[1][2]

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).[3]

K2P13.1 was first discovered in 2000 from a rat cDNA library, along with the closely related protein K2P12.1[1] 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.[1][4] Later research showed that THIK-1 can be activated by G-protein-coupled receptor pathways[5] and by polyanionic lipids such as PIP2 and oleoyl-CoA.[6]

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.[7] THIK-1 activity can regulate microglial ramification, surveillance, NLRP3 inflammasome activation, and subsequent release of pro-inflammatory cytokine interleukin-1β (IL-1β).[8][9][10] It also plays a role in cell shrinkage during apoptosis via caspase-8 cleavage.[11]

See also

  • Tandem pore domain potassium channel

References

  1. ↑ 1.0 1.1 1.2 "THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels". The Journal of Biological Chemistry 276 (10): 7302–7311. March 2001. doi:10.1074/jbc.M008985200. PMID 11060316. 
  2. ↑ "International Union of Pharmacology. LV. Nomenclature and molecular relationships of two-P potassium channels". Pharmacological Reviews 57 (4): 527–540. December 2005. doi:10.1124/pr.57.4.12. PMID 16382106. https://escholarship.org/uc/item/3k15p5vt. 
  3. ↑ "CryoEM Structure of the human THIK-1 K2P K+ Channel Reveals a Lower 'Y-gate' Regulated by Lipids and Anaesthetics" (in en). bioRxiv. 2024-06-27. doi:10.1101/2024.06.26.600475. https://www.biorxiv.org/content/10.1101/2024.06.26.600475v1. Retrieved 2024-12-04. 
  4. ↑ "Two-Pore Domain Potassium Channel in Neurological Disorders" (in en). The Journal of Membrane Biology 254 (4): 367–380. 2021-08-01. doi:10.1007/s00232-021-00189-8. ISSN 1432-1424. PMID 34169340. https://link.springer.com/article/10.1007/s00232-021-00189-8. 
  5. ↑ "Regulation of the two-pore domain potassium channel, THIK-1 and THIK-2, by G protein coupled receptors" (in en). PLOS ONE 18 (4). 2023-04-26. doi:10.1371/journal.pone.0284962. ISSN 1932-6203. PMID 37099539. Bibcode: 2023PLoSO..1884962T. 
  6. ↑ "The versatile regulation of K2P channels by polyanionic lipids of the phosphoinositide and fatty acid metabolism" (in en). The Journal of General Physiology 154 (2). 2022-02-07. doi:10.1085/jgp.202112989. ISSN 0022-1295. PMID 34928298. PMC 8693234. https://rupress.org/jgp/article/154/2/e202112989/212926/The-versatile-regulation-of-K2P-channels-by. 
  7. ↑ "Differential contribution of THIK-1 K+ channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia". Journal of Neuroinflammation 21 (1): 58. 2024-02-26. doi:10.1186/s12974-024-03042-6. ISSN 1742-2094. PMID 38409076. 
  8. ↑ "Microglial Ramification, Surveillance, and Interleukin-1β Release Are Regulated by the Two-Pore Domain K+ Channel THIK-1" (in en). Neuron 97 (2): 299–312.e6. January 2018. doi:10.1016/j.neuron.2017.12.002. PMID 29290552. 
  9. ↑ "Distinct Molecular Mechanisms Underlying Potassium Efflux for NLRP3 Inflammasome Activation" (in English). Frontiers in Immunology 11. 2020-12-07. doi:10.3389/fimmu.2020.609441. ISSN 1664-3224. PMID 33424864. 
  10. ↑ "The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation" (in en). Glia 70 (7): 1301–1316. 2022. doi:10.1002/glia.24174. ISSN 1098-1136. PMID 35353387. 
  11. ↑ "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. 2016-11-01. doi:10.1016/j.bbamcr.2016.08.010. ISSN 0167-4889. PMID 27566292. https://linkinghub.elsevier.com/retrieve/pii/S0167488916302154. 

Further reading



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