| KCNK4 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | KCNK4 , K2p4.1, TRAAK, TRAAK1, potassium two pore domain channel subfamily K member 4, FHEIG | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 605720; MGI: 1298234; HomoloGene: 7391; GeneCards: KCNK4; OMA:KCNK4 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Potassium channel subfamily K member 4 is a protein that in humans is encoded by the KCNK4 gene. [5] [6] [7] KCNK4 protein channels are also called TRAAK channels.
KNCK4 is a gene segment that encodes for the TRAAK (TWIK-related Arachidonic Acid-Stimulated K+) subfamily of mechanosensitive potassium channels. Potassium channels play a role in many cellular processes including action potential depolarization, muscle contraction, hormone secretion, osmotic regulation, and ion flow. The K2P4.1 protein is a lipid-gated ion channel that belongs to the superfamily of potassium channel proteins containing two pore-forming P domains (K2P). K2P4.1 homodimerizes and functions as an outwardly rectifying channel. It is expressed primarily in neural tissues and is stimulated by membrane stretch and polyunsaturated fatty acids. [7]
TRAAK channels are found in mammalian neurons and are part of a protein family of weakly inward rectifying potassium channels. This subfamily of potassium channels is mechanically gated. The C-terminal of TRAAK has a charged cluster that is important in maintaining the mechanosensitive properties of the channel. [8]
TRAAK is only expressed in neuronal tissue, and can be found in the brain, spinal cord, and retina, which suggests that it has a function beyond mechanotransduction in terms of neuronal excitability. [9] The highest levels of TRAAK expression are in the olfactory system, cerebral cortex, hippocampal formation, habenula, basal ganglia, and cerebellum. [9] TRAAK channels are mechanically activated when there is a convex curvature in the membrane that alters the channel’s activity. TRAAK channels are thought to have a role in axonal pathfinding, growth cone motility, and neurite elongation, as well as possibly having a role in touch or pain detection. [10] [11]
TRAAK channels play a critical role in the maintenance of the resting membrane potential in excitable cell types. [12] More recently, TRAAK channels have been identified as an integral component of the nervous system, contributing to a variety of important biological functions such as: neurite migration, neurotransmission, and signal transduction across several sensory modalities. [13] TRAAK and related mechanosensitive ion channels initiate these and other complex physiological processes by detecting asymmetrical pressure gradients generated across the inner and outer leaflets of the cell membrane, characterizing a rich profile of mechanical bilayer interactions. [14] Furthermore, KCNK4 expression patterns the axonal segments of neurons in both central and peripheral nervous systems by inserting TRAAK membrane protein channels at the Nodes of Ranvier and allowing for saltatory conduction. [15] The pathologies that are associated with improper KCNK4 expression such as Hirchsprung's Disease and FHEIG (facial dysmorphism, hypertrichosis, epilepsy, developmental/ID delay, and gingival overgrowth) syndrome, manifest accordingly as a constellation of neurological symptoms resulting from neuronal dysplasia. [16] [17] Animal models containing known syndromic KCNK4 mutations have recapitulated these phenotypic abnormalities. [18] High TRAAK channel density has also been implicated in the resulting cerebral ischemia following the event of a stroke. [19]
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 cell functions.
Potassium voltage-gated channel subfamily A member 1 also known as Kv1.1 is a shaker related voltage-gated potassium channel that in humans is encoded by the KCNA1 gene. Isaacs syndrome is a result of an autoimmune reaction against the Kv1.1 ion 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 including signaling lipids, oxygen tension, pH, mechanical stretch, and G-proteins. Two-pore-domain potassium channels correspond structurally to a inward-rectifier potassium channel α-subunits. Each inward-rectifier potassium channel α-subunit is composed of two transmembrane α-helices, a pore helix and a potassium ion selectivity filter sequence and assembles into a tetramer forming the complete channel. The two-pore domain potassium channels instead are dimers where each subunit is essentially two α-subunits joined together.
The Kir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene.
Potassium voltage-gated channel subfamily E member 1 is a protein that in humans is encoded by the KCNE1 gene.
K+ channel tetramerisation domain is the N-terminal, cytoplasmic tetramerisation domain (T1) of voltage-gated K+ channels. It defines molecular determinants for subfamily-specific assembly of alpha-subunits into functional tetrameric channels. It is distantly related to the BTB/POZ domain Pfam PF00651.
Potassium voltage-gated channel, Shab-related subfamily, member 1, also known as KCNB1 or Kv2.1, is a protein that, in humans, is encoded by the KCNB1 gene.
Potassium channel subfamily K member 2, also known as TREK-1, is a protein that in humans is encoded by the KCNK2 gene.
Potassium channel subfamily K member 3 is a protein that in humans is encoded by the KCNK3 gene.
ATP-sensitive inward rectifier potassium channel 10 is a protein that in humans is encoded by the KCNJ10 gene.
Potassium channel subfamily K member 1 is a protein that in humans is encoded by the KCNK1 gene.
Potassium channel subfamily K member 9 is a protein that in humans is encoded by the KCNK9 gene.
Potassium channel subfamily K member 5 is a protein that in humans is encoded by the KCNK5 gene.
G protein-activated inward rectifier potassium channel 3 is a protein that in humans is encoded by the KCNJ9 gene.
Potassium channel, subfamily K, member 7, also known as KCNK7 or K2P7.1 is a protein which is encoded in humans by the KCNK7 gene. K2P7.1 is a potassium channel containing two pore-forming P domains. Multiple transcript variants encoding different isoforms have been found for this gene.
Potassium channel, subfamily K, member 10, also known as KCNK10 is a human gene. The protein encoded by this gene, K2P10.1, is a potassium channel containing two pore-forming P domains.
Potassium channel subfamily K member 16 is a protein that in humans is encoded by the KCNK16 gene. The protein encoded by this gene, K2P16.1, is a potassium channel containing two pore-forming P domains.
Potassium channel blockers are agents which interfere with conduction through potassium channels.
A potassium channel opener is a type of drug which facilitates ion transmission through potassium channels.
Mechanosensitive channels (MSCs), mechanosensitive ion channels or stretch-gated ion channels are membrane proteins capable of responding to mechanical stress over a wide dynamic range of external mechanical stimuli. They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. They are the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis (e.g. thirst). The channels vary in selectivity for the permeating ions from nonselective between anions and cations in bacteria, to cation selective allowing passage Ca2+, K+ and Na+ in eukaryotes, and highly selective K+ channels in bacteria and eukaryotes.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
