Potassium channel subfamily K member 2, also known as TREK-1, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''KCNK2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
This gene encodes K
2P2.1, a
lipid-gated ion channel belonging to the two-pore-domain background potassium channel protein family. This type of potassium channel is formed by two homodimers that create a channel that releases potassium out of the cell to control resting membrane potential. The channel is opened by anionic lipid, certain anesthetics, membrane stretching, intracellular acidosis, and heat. Three transcript variants encoding different isoforms have been found for this gene.
Function in neurons
TREK-1 is part of the subfamily of mechano-gated
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 cel ...
s that are present in mammalian neurons. They can be gated in both chemical and physical ways and can be opened via both physical stimuli and chemical stimuli. TREK-1 channels are found in a variety of tissues, but are particularly abundant in the brain and heart and are seen in various types of neurons. The
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
of TREK-1 channels plays a role in the mechanosensitivity of the channels.
In the neurons of the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
, TREK-1 channels are important in physiological, pathophysiological, and pharmacological processes, including having a role in
electrogenesis,
ischemia
Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems wi ...
, and
anesthesia
Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...
. TREK-1 has an important role in neuroprotection against
epilepsy
Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
and brain and
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spi ...
ischemia and is being evaluated as a potential target for new developments of therapeutic agents for neurology and anesthesiology.
In the absence of a properly functioning
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
, TREK-1 channels can still open via mechanical gating.
The
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
functions independently of the cytoskeleton and the thickness and curvature of the membrane is able to modulate the activity of the TREK-1 channels. The change in thickness is thought to be sensed by an amphipathic helix that extends from the inner leaflet of the membrane.
The insertion of certain compounds into the membrane, including inhaled anesthetics and propofol, activate TREK-1 through the enzyme phospholipase D2 (PLD2). Prior to the addition of anesthetic, PLD2 associates with GM-1 lipid rafts. After anesthetic, the enzyme or a complex of the enzyme and the channel traffic to PIP2 domains where the enzyme makes phosphatidic acid that opens the channel.
See also
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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 including ...
References
Further reading
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External links
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{{Ion channels, g3
Ion channels