Potassium channel subfamily K member 4 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 ''KCNK4''

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 ...

. KCNK4 protein channels are also called TRAAK channels.

Function

''KNCK4'' is a gene segment that encodes for the TRAAK (TWIK-related Arachidonic Acid-Stimulated K+) subfamily of mechanosensitive potassium channels.

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 ...

s play a role in many cellular processes including

action potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

depolarization,

muscle contraction Muscle contraction is the activation of Tension (physics), tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in musc ...

, hormone secretion, osmotic regulation, and ion flow. The K_2P4.1 protein is a

lipid-gated ion channel Lipid-gated ion channels are a class of ion channels whose conductance of ions through the membrane depends directly on lipids. Classically the lipids are membrane resident anionic signaling lipids that bind to the transmembrane domain on the inn ...

that belongs to the superfamily of potassium channel proteins containing two pore-forming P domains (K_2P). K_2P4.1 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. 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 The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy 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 t ...

of TRAAK has a charged cluster that is important in maintaining the mechanosensitive properties of the channel. TRAAK is only expressed in neuronal tissue, and can be found in the

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

, and

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

, which suggests that it has a function beyond mechanotransduction in terms of neuronal excitability. The highest levels of TRAAK expression are in the

olfactory system The olfactory system, is the sensory nervous system, sensory system used for the sense of smell (olfaction). Olfaction is one of the special senses directly associated with specific organs. Most mammals and reptiles have a main olfactory system ...

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

hippocampal formation The hippocampal formation is a compound structure in the medial temporal lobe of the brain. It forms a c-shaped bulge on the floor of the inferior horn of the lateral ventricle. Typically, the hippocampal formation is said to included the dent ...

, habenula,

basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

, and

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

. 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 A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago ...

motility, and

neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...

elongation, as well as possibly having a role in touch or pain detection. TRAAK channels play a critical role in the maintenance of the

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 ...

in excitable cell types. 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 Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

across several sensory modalities. 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. 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 Nodes of Ranvier ( ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated axonal domains that are high in sodium and potassium ion channels ...

and allowing for

saltatory conduction In neuroscience, saltatory conduction () is the propagation of action potentials along myelinated axons from one node of Ranvier to the next, increasing the conduction velocity of action potentials. The uninsulated nodes of Ranvier are the on ...

. 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. Animal models containing known syndromic ''KCNK4'' mutations have recapitulated these phenotypic abnormalities. High TRAAK channel density has also been implicated in the resulting cerebral ischemia following the event of a stroke.

References

External links

* {{Ion channels, g3 Ion channels

Function

See also

References

Further reading

External links