Aquaporins, also called water channels, are channel proteins from a larger family of major intrinsic proteins that form pores in the membrane of biological cells, mainly facilitating transport of water between cells.
The cell membranes of a variety of different cells contain aquaporins through which water can flow more rapidly into and out of the cell than by diffusing through the phospholipid bilayer.
AQP4 is an integral member of the water channel protein expressed by many cell types including: gastrointestinal, lung, retinal, renal, and muscle cells.
AQP4 is expressed on astrocytic in feet that abut endothelial cells, which form the glia limitans component of the blood brain barrier.
When the barrier is breached, or in areas such as the area posttema where it is lacking, circulating AQP4 – IgG gains access and bonds to its target antigen initiating inflammatory responses that generate neuromyelitis optica spectrum disorder lesions.
Aquaporins are usually always open and are prevalent in about every cell type.
Water passes through the cell membrane through simple diffusion because it is a small molecule, and through osmosis.
Passage through osmosis occurs when the concentration of water outside of the cell is greater than that of the inside.
Water is a polar molecule making simple diffusion a relatively slow process, and in tissues with high water permeability the majority of water passes through aquaporin.
In most cells, water moves in and out by osmosis through the lipid component of cell membranes.
Genetic defects involving aquaporin genes have been associated with nephrogenic diabetes insipidus and neuromyelitis optica.
Water channels are effectively proteins.
Pores can allow water to pass without the passage of small solutes.
Aquaporins selectively conduct water molecules in and out of the cell, while preventing the passage of ions and other solutes.
Aquaporin water channels, are integral membrane pore proteins.
Some aquaglyceroporins, also transport other small uncharged dissolved molecules including ammonia, CO2, glycerol, and urea: aquaporin 3 channel has a pore width of 8–10 Ångströms and allows the passage of hydrophilic molecules ranging between 150 and 200 Da.
Water pores completely block ions including protons, essential to conserve the membrane’s electrochemical potential difference.
Water molecules traverse through the pore of the channel in single file.
Aquaporin proteins are composed of a bundle of six transmembrane α-helices,
which are embedded in the cell membrane.
The ar/R selectivity filter is a cluster of amino acids enabling the aquaporin to selectively let through or block the passage of different molecules.
Aquaporins form tetramers in the cell membrane.
Different aquaporins have different sized water channels, the smallest types allowing nothing but water through.
X-ray profiles show that aquaporins have two conical entrances.
The aromatic/arginine or “ar/R” selectivity filter is a cluster of amino acids that help bind to water molecules and exclude other molecules that may try to enter the pore: it is able to selectively bind water molecules, allowing them through, and prevent other molecules from entering.
The ar/R filter weakens the hydrogen bonds between water molecules, enabling the arginines, which carry a positive charge, to interact with the water molecules and to filter out undesirable protons.
There are thirteen known types of aquaporins in mammals, and six of these are located in the kidney.
Type Location Function
Aquaporin 1
kidney
proximal convoluted tubule
proximal straight tubule
thin descending loop of Henle
Water reabsorption
Aquaporin 2
kidney
connecting tubule
cortical collecting duct
outer medullary collecting duct
inner medullary collecting duct
Water reabsorption in response to ADH
Aquaporin 3
kidney (basolaterally)
connecting tubule
cortical collecting duct
outer medullary collecting duct
Water reabsorption and glycerol permeability
Aquaporin 4
kidney (basolaterally)
inner medullary collecting duct
Water reabsorption
Aquaporin-1 (AQP1) is found in choroid plexus, contributes to production of CSF.
AQP4 is found on perivascular and ependymal cells.
Mutations in the aquaporin-2 gene cause hereditary nephrogenic diabetes insipidus in humans.
Rarely people are identified with severe or total deficiency in aquaporin-1.
They exhibit a defect in the ability to concentrate solutes in the urine and to conserve water when deprived of drinking water.
Aquaporin’s play a role in genetically determined nephrogenic diabetes insipidus, and in acquired forms of nephrogenic diabetes insipidus causing increased urine production).
Aquaporin 2 is regulated by vasopressin which, and when activated results in aquaporin-2 containing vesicles to increase water uptake and return to circulation.
Mutation of the aquaporin 2 vasopressin receptor is a cause of acquired diabetes insipidus.
Autoimmune reactions against aquaporin 4 in humans produce Devic’s disease (neuromyelitis optical spectrum disorder).
Eculizumab injection for intravenous use for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.