Recent Advances in Water Transport
| Title: | Recent Advances in Water Transport |
|---|---|
| Author: | Zeidel, Mark L. |
| Publisher: | Seminars in Nephrology |
| Date Published: | March 01, 1998 |
| Reference Number: | 388 |
Complex organisms regulate the osmolalities of their compartments by limiting water flow across some membranes and promoting rapid water flow across others via proteins called aquaporins. Barrier epithelia limit water flow by reducing the mobilities of fatty acid chains in their apical membranes, especially in the outer leaflets of these membranes. Aquaporins are 28 to 30 kDa, 6 membrane-spanning proteins that are expressed in a wide variety of organisms from bacteria to plants to mammals. The structural and biophysical data are summarized to develop our best understanding of water pore function. In addition, the regulation of trafficking of AQP 2 into and out of the apical membranes of collecting duct principal cells is described.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
© Copyright NDI Foundation 2007 (JC)
The cell membranes that act as barriers to water permeability do so because of their structure. The membranes are composed of lipid bilayers: a layer of phosphate head groups that provide little or no barrier to water flow on top of a lipid layer containing long hydrocarbon chains that water finds difficult to cross. There is an intervening segment followed by another bilayer of lipids and phosphate head groups.
It requires a lot of energy to get through the lipid section of the bilayer, so few water molecules are within the hydrocarbon phase at any one time. Once the water molecules do get through the first bilayer of the membrane, they have to enter the central region of the membrane where the ends of the hydrocarbon chains meet with the ends of the hydrocarbon chains of the second lipid bilayer. Once the water molecules get through this second lipid bilayer (generally by entering a defect between the hydrocarbon chains), they enter the second phosphate head group layer. This layer, like the first phosphate head group, offers little resistance to the water molecules.
Apical membranes can reduce water permeability further by combining with sphingomyelin and cholesterol to rigidify the outermost facing section of the bilayer. It may also be that the apical membrane has a smaller surface area than the basolateral membrane.
AQPs are found in animals and plants. Nine different types have been found in humans (AQP0 - AQP8). Some of the AQPs are distributed widely throughout the body, others are more localized. Some only let water pass through them and some allow small solutes to pass through as well. Some AQPs are constitutive, i.e. they operate independently of any hormonal signal. Others are regulated, i.e. they operate when signaled to do so by a hormone.
Classic functional theory describes AQPs as being able to form a cylinder-like pore that is long enough to reach through the apical membrane and so narrow that water molecules can only pass through the pore in single-file. However, this classical formulation may not be applicable to all AQPs as some conduct more water than the mathematical model of the classical theory can account for. Further, some AQPs allow small solutes to travel through them.
Aquaporin-2 (AQP2) is an AQP localized in the kidney inner medullary collecting duct (IMCD). It plays a very important role in the kidney's urine concentrating process, and the manner in which it is regulated by the antidiuretic hormone, arginine vasopressin is fairly well understood. When AVP binds with its vasopressin-2 receptor on the basolateral membrane, it stimulates the adenylyl cyclase enzyme system via a Gs protein. This acts to elevate levels of cAMP. cAMP activates protein kinase A, which phosphorylates AQP2. This phosophorylation (introducing a phosphate group to the AQP2) leads to the insertion of AQP2-containing vesicles into the apical membrane. Once the AQP2s are inserted in the apical membrane, much more water can flow through the membrane via the AQP2s. This increased water permeability ends when AVP absents itself from the cell and the AQP2s are retrieved from the membrane and brought back inside the cell in sacs called endosomes. (There seems to be 5,200 AQP2s per endosome in endosomes derived from toad bladder and rat kidney.)
AVP regulates both the synthesis and trafficking of AQP2. cAMP activates transcription of AQP2, leading to increases in its synthesis. Conditions that inhibit AVP action, such as ureteral obstruction and lithium exposure, can reduce AQP2 synthesis and trafficking. Urinary calcium can regulate AQP2 function. When there is a high level of urinary calcium, it can bind to calcium receptors in the IMCD. This triggers the removal of AQP2 from the apical membrane, reducing the ability of the kidney to concentrate urine. Researchers view this process as a mechanism that protects against calcium stone formation in the kidney.