KCNK13
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Potassium channel, subfamily K, member 13 (KCNK13), also known as K2P13.1 or THIK-1, is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''KCNK13''
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
. It is a
potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of ...
containing two pore-forming P domains.


Function

K2P13.1 was first discovered in 2000 from a rat
cDNA library A cDNA library is a combination of cloned cDNA (complementary DNA) fragments inserted into a collection of host cells, which constitute some portion of the transcriptome of the organism and are stored as a "library". cDNA is produced from fully t ...
, along with the closely related protein K2P12.1 The two channels were named tandem pore domain halothane-inhibited K+ channel 1 and 2 (THIK-1 and THIK-2) because the
anesthetic An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into t ...
halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful ...
inhibited the potassium current. THIK-1 was also shown to be activated by
arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...
and displayed mild voltage dependence, with moderate outward rectification at low external K+ and weak inward rectification with nearly symmetrical K+ concentrations. Later research showed that THIK-1 can be activated by
G-protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...
pathways and by polyanionic
lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
s such as PIP2 and oleoyl-CoA. In humans, THIK-1 expression is almost exclusively restricted to
microglia Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...
, where it functions as the main
potassium channel Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of ...
and is responsible for maintaining their
resting membrane potential The relatively static membrane potential of quiescent cells is called the resting membrane potential (or resting voltage), as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential. The re ...
through tonic background potassium conductance. THIK-1 activity can regulate microglial ramification, surveillance,
NLRP3 NLR family pyrin domain containing 3 (NLRP3) (previously known as NACHT, LRR, and PYD domains-containing protein 3 ALP3and cryopyrin), is a protein that in humans is encoded by the ''NLRP3'' gene located on the long arm of chromosome 1. NLRP ...
inflammasome Inflammasomes are cytosolic multiprotein complexes of the innate immune system responsible for the activation of inflammatory responses and cell death. They are formed as a result of specific cytosolic pattern recognition receptors (PRRs) sens ...
activation, and subsequent release of pro-inflammatory cytokine interleukin-1β (IL-1β). It also plays a role in cell shrinkage during apoptosis via caspase-8 cleavage.


See also

*
Tandem pore domain potassium channel The two-pore-domain or tandem pore domain potassium channels are a family of 15 members that form what is known as leak channels which possess Goldman-Hodgkin-Katz (open) rectification. These channels are regulated by several mechanisms includi ...


References


Further reading

* * * *


External links

* Ion channels {{membrane-protein-stub