Chloride channel
Encyclopedia
Chloride channels are a superfamily of poorly understood ion channel
s consisting of approximately 13 members.
Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups. The importance of one such group, the CLC family of chloride channels, can be seen from the diseases that develop when the channel does not function normally.
This family of ion channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three CLC subfamilies are found in animals. CLC-1 is involved in setting and
restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney [3]. These proteins contain two CBS domain
s. Chloride channels are also important for maintaining safe ion
concentrations within plant cells.
, is due to the defective transport of chloride ions and associated ions in the thick ascending loop of Henle. CLCNKB
has been implicated.
Another inherited disease that affects the kidney organs is Dent's Disease
, characterised by low molecular weight proteinuria and hypercalciuria where mutations in CLCN5
are implicated.
Thomsen disease
is associated with dominant mutations and Becker disease with recessive mutations in CLCN1
.
Cystic fibrosis
is caused by a mutation in the DF508 region of the CFTR
gene, which prevents the proper folding of the protein and subsequent degradation, resulting in decreased numbers of chloride channels in the body. This causes the build up of mucus in the body and chronic infections.
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s consisting of approximately 13 members.
Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation. Based on sequence homology the chloride channels can be subdivided into a number of groups. The importance of one such group, the CLC family of chloride channels, can be seen from the diseases that develop when the channel does not function normally.
This family of ion channels contains 10 or 12 transmembrane helices. Each protein forms a single pore. It has been shown that some members of this family form homodimers. In terms of primary structure, they are unrelated to known cation channels or other types of anion channels. Three CLC subfamilies are found in animals. CLC-1 is involved in setting and
restoring the resting membrane potential of skeletal muscle, while other channels play important parts in solute concentration mechanisms in the kidney [3]. These proteins contain two CBS domain
CBS domain
The CBS domain is a protein domain found in a range of proteins in all species from bacteria to man. It was first identified as a conserved sequence region in 1997 and named after cystathionine beta synthase, one of the proteins it is found in...
s. Chloride channels are also important for maintaining safe ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
concentrations within plant cells.
Pathology
Bartter's syndrome, which is associated with renal salt wasting and hypokalemic alkalosisAlkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...
, is due to the defective transport of chloride ions and associated ions in the thick ascending loop of Henle. CLCNKB
CLCNKB
Chloride channel Kb, also known as CLCNKB, is a protein which in humans is encoded by the CLCNKB gene.Chloride channel Kb is a member of the CLC family of voltage-gated chloride channels, which comprises at least 9 mammalian chloride channels. Each is believed to have 12 transmembrane domains and...
has been implicated.
Another inherited disease that affects the kidney organs is Dent's Disease
Dent's disease
Dent's disease is a rare X-linked recessive inherited condition that affects the proximal renal tubules of the kidney. It is one cause of Fanconi syndrome, and is characterized by tubular proteinuria, hypercalciuria, calcium nephrolithiasis, nephrocalcinosis and chronic renal failure."Dent's...
, characterised by low molecular weight proteinuria and hypercalciuria where mutations in CLCN5
CLCN5
H/Cl exchange transporter 5 is a protein that in humans is encoded by the CLCN5 gene.- External links :...
are implicated.
Thomsen disease
Thomsen disease
Thomsen disease, a form of Myotonia congenita, is a muscular genetic disorder characterized by muscle stiffness and an inability of the muscle to relax after a voluntary contraction...
is associated with dominant mutations and Becker disease with recessive mutations in CLCN1
CLCN1
Chloride channel protein, skeletal muscle is a protein that in humans is encoded by the CLCN1 gene. Mutations in this protein cause congenital myotonia....
.
Cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
is caused by a mutation in the DF508 region of the CFTR
Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes...
gene, which prevents the proper folding of the protein and subsequent degradation, resulting in decreased numbers of chloride channels in the body. This causes the build up of mucus in the body and chronic infections.
Functions
Chloride channels are important for setting cell resting membrane potential and maintaining proper cell volume. These channels conduct Cl- as well as other anions such as HCO3-, I-, SCN-, and NO3-. The structure of these channels are not like other known channels. Chloride channel subunits contain between 1 and 12 transmembrane segments. Some members of this family are activated by voltage, while others are activated by Ca2+, extracellular ligands, and pH among other modulators.Commercial Applications
Some organic materials disrupt chloride channels in fleas, causing death. Selamectin is the active ingredient in Revolution, a topical insecticide and antihelminthic used on dogs and cats. Selamectin works by replacing glutamate which normally interacts with receptors that open chloride channels at muscle synapses found in parasites. Unlike glutamate, selamectin activates the chloride current without desensitization, thereby producing prolonged hyperpolarization and impaired muscle contraction.Human genes
- CLCA1CLCA1Calcium-activated chloride channel regulator 1 is a protein that in humans is encoded by the CLCA1 gene....
, CLCA2, CLCA3CLCA3Chloride channel, calcium activated, family member 3, also known as CLCA3, is a protein which in humans is encoded by the CLCA3P pseudogene. The protein encoded by this gene is a chloride channel...
, CLCA4CLCA4Chloride channel, calcium activated, family member 4, also known as CLCA4, is a protein which in humans CLCA4 gene. The protein encoded by this gene is a chloride channel. Protein structure prediction methods suggest the N-terminal region of CLCA4 protein is a zinc metalloprotease, and the protein... - CLCN1CLCN1Chloride channel protein, skeletal muscle is a protein that in humans is encoded by the CLCN1 gene. Mutations in this protein cause congenital myotonia....
, CLCN2CLCN2Chloride channel protein 2 is a protein that in humans is encoded by the CLCN2 gene. Mutations of this gene have been found to cause Idiopathic generalised epilepsy . CLCN2 contains a transmembrane region that is involved in chloride ion transport as well two intracellular copies of the CBS domain....
, CLCN3CLCN3H/Cl exchange transporter 3 is a protein that in humans is encoded by the CLCN3 gene....
, CLCN4CLCN4H/Cl exchange transporter 4 is a protein that in humans is encoded by the CLCN4 gene....
, CLCN5CLCN5H/Cl exchange transporter 5 is a protein that in humans is encoded by the CLCN5 gene.- External links :...
, CLCN6CLCN6Chloride transport protein 6 is a protein that in humans is encoded by the CLCN6 gene....
, CLCN7CLCN7Chloride channel 7, also known as CLCN7, is a human gene. In melanocytic cells this gene is regulated by the Microphthalmia-associated transcription factor.-External Links:*...
, CLCNKACLCNKAChloride channel protein ClC-Ka is a protein that in humans is encoded by the CLCNKA gene....
, CLCNKBCLCNKBChloride channel Kb, also known as CLCNKB, is a protein which in humans is encoded by the CLCNKB gene.Chloride channel Kb is a member of the CLC family of voltage-gated chloride channels, which comprises at least 9 mammalian chloride channels. Each is believed to have 12 transmembrane domains and... - CLIC1CLIC1Chloride intracellular channel protein 1 is a protein that in humans is encoded by the CLIC1 gene.-Further reading:-External links:...
, CLIC2CLIC2Chloride intracellular channel protein 2 is a protein that in humans is encoded by the CLIC2 gene....
, CLIC3CLIC3Chloride intracellular channel protein 3 is a protein that in humans is encoded by the CLIC3 gene. This protein is a chloride channel....
, CLIC4CLIC4Chloride intracellular channel 4, also known as CLIC4, is a eukaryotic gene.- Binding partners :CLIC4 binds to dynamin I, α-tubulin, β-actin, creatine kinase and two 14-3-3 isoforms.-Further reading:...
, CLIC5CLIC5Chloride intracellular channel protein 5 is a protein that in humans is encoded by the CLIC5 gene.- Function :Chloride intracellular channels are involved in chloride ion transport within various subcellular compartments. CLIC5 specifically associates with the cytoskeleton of placenta microvilli...
, CLIC6CLIC6Chloride intracellular channel protein 6 is a protein that in humans is encoded by the CLIC6 gene.-Interactions:CLIC6 has been shown to interact with Dopamine receptor D3....