9jh1

Structural highlights

Function

KCNKD_HUMAN K(+) channel that conducts outward rectifying tonic currents potentiated by purinergic signals (PubMed:24163367, PubMed:25148687, PubMed:30472253, PubMed:38409076). Homo- and heterodimerizes to form functional channels with distinct regulatory and gating properties (PubMed:25148687). Contributes most of K(+) currents at the plasma membrane of resting microglia. Maintains a depolarized membrane potential required for proper ramified microglia morphology and phagocytosis, selectively mediating microglial pruning of presynaptic compartments at hippocampal excitatory synapses (PubMed:38409076). Upon local release of ATP caused by neuronal injury or infection, it is potentiated by P2RY12 and P2RX7 receptor signaling and contributes to ATP-triggered K(+) efflux underlying microglial NLRP3 inflammasome assembly and IL1B release (By similarity) (PubMed:38409076).[UniProtKB:Q8R1P5]^{[1] [2] [3] [4]}

References

1. ↑ Chatelain FC, Bichet D, Feliciangeli S, Larroque MM, Braud VM, Douguet D, Lesage F. Silencing of the tandem pore domain halothane-inhibited K+ channel 2 (THIK2) relies on combined intracellular retention and low intrinsic activity at the plasma membrane. J Biol Chem. 2013 Dec 6;288(49):35081-92. PMID:24163367 doi:10.1074/jbc.M113.503318
2. ↑ Blin S, Chatelain FC, Feliciangeli S, Kang D, Lesage F, Bichet D. Tandem pore domain halothane-inhibited K+ channel subunits THIK1 and THIK2 assemble and form active channels. J Biol Chem. 2014 Oct 10;289(41):28202-12. PMID:25148687 doi:10.1074/jbc.M114.600437
3. ↑ Staudacher I, Seehausen S, Gierten J, Illg C, Schweizer PA, Katus HA, Thomas D. Cloning and characterization of zebrafish K(2P)13.1 (THIK-1) two-pore-domain K(+) channels. J Mol Cell Cardiol. 2019 Jan;126:96-104. PMID:30472253 doi:10.1016/j.yjmcc.2018.11.013
4. ↑ Rifat A, Ossola B, Bürli RW, Dawson LA, Brice NL, Rowland A, Lizio M, Xu X, Page K, Fidzinski P, Onken J, Holtkamp M, Heppner FL, Geiger JRP, Madry C. Differential contribution of THIK-1 K(+) channels and P2X7 receptors to ATP-mediated neuroinflammation by human microglia. J Neuroinflammation. 2024 Feb 26;21(1):58. PMID:38409076 doi:10.1186/s12974-024-03042-6