Potassium channel, subfamily K, member 13 (KCNK13), also known as K2P13.1 or THIK-1, is aprotein that in humans is encoded by theKCNK13gene. It is apotassium channel containing two pore-forming P domains.[5][6]
Ribbon structure of homodimeric two-pore potassium channel K2P13 (THIK-1).[7]
K2P13.1 was first discovered in 2000 from a ratcDNA library, along with the closely related proteinK2P12.1[5] The two channels were named tandem pore domain halothane-inhibited K+ channel 1 and 2 (THIK-1 and THIK-2) because theanesthetichalothane inhibited the potassium current. THIK-1 was also shown to be activated byarachidonic acid and displayed mild voltage dependence, with moderate outward rectification at low external K+ and weakinward rectification with nearly symmetrical K+ concentrations.[5][8] Later research showed that THIK-1 can be activated byG-protein-coupled receptor pathways[9] and by polyanioniclipids such asPIP2 andoleoyl-CoA.[10]
In humans, THIK-1 expression is almost exclusively restricted tomicroglia, where it functions as the mainpotassium channel and is responsible for maintaining theirresting membrane potential through tonic background potassium conductance.[11] THIK-1 activity can regulate microglial ramification, surveillance,NLRP3inflammasome activation, and subsequent release of pro-inflammatory cytokineinterleukin-1β (IL-1β).[12][13][14] It also plays a role in cell shrinkage during apoptosis via caspase-8 cleavage.[15]
^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".bioRxiv10.1101/2024.06.26.600475.
