Renal Aquaporins
| Title: | Renal Aquaporins |
|---|---|
| Authors: | Knepper, Mark; Wade, James B.; Terris, Ph.D., James M.; Ecelbarger, Ph.D., Carolyn; Marples, David; Mandon, Beatrice; Chou, Chung-Lin; Kishore, Bellamkonda K.; Nielsen, Soren |
| Publisher: | Kidney International |
| Date Published: | June 01, 1996 |
| Reference Number: | 383 |
Aquaporins (AQPs) are a newly recognized family of transmembrane proteins that function as molecular water channels. At least four aquaporins are expressed in the kidney where they mediate rapid water transport across water permeable epithelia and play critical roles in urinary concentrating and diluting processes. AQP1 is constitutively expressed at extremely high levels in the proximal tubule and descending limb of Henle's loop. AQP2, -3 and -4 are expressed predominantly in the collecting duct system. AQP2 is the predominant water channel in the apical plasma membrane and AQP3 and -4 are found in the basolateral plasma membrane. Short-term regulation of collecting duct water permeability by vasopressin is largely a consequence of regulated trafficking of AQP2-containing vesicles to and from the apical plasma membrane.
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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)
A family of intrinsic membrane proteins called aquaporins (AQPs) that act as channels through which water can flow across cell membranes help make it possible for nephron and the kidney tissue that surrounds it (the interstitium) to create the required osmotic conditions for urine concentration. AQPs allow the cell membranes they locate in to become much more water permeable than they would be without them. This allows more body water to flow through the cells than would otherwise. Some AQPs are expressed constitutively. That is, they are in the membrane and operate independently of any hormone. Other AQPs are regulated by hormones, not entering its target membrane or operating as a water channel to make the membrane more water permeable until signaled to do so by a hormone. In this article, Knepper, et al., discuss the location and role of AQPs 1, 2, 3 and 4.
In the kidney, AQP1 is located in the descending loop of Henle. There it is constitutively expressed, allowing extremely rapid water transport across the descending limb cells. So far, it is the only AQP known to be expressed in this segment of the nephron. The extremely high levels of expression, greater than 20 million copies per cell in the rat descending limb of Henle, correlate well with the very high degree of water permeability found in these nephron segments. AQP1 is found in both the apical and basolateral cell membranes. (If you picture the cell as an upright rectangle, and the membrane as the rectangle's perimeter, the top of the rectangle is the apical membrane, and the bottom and sides form the basolateral membrane.)
Aquaporins 2, 3 and 4 are located in the principal cells of the CD and inner medullary CD cells. AQP2s are located in the apical region of these cells, while AQPs 3 and 4 are located in the basolateral membranes. There is a predominance of AQP3 in the lateral membrane and a nearly equal distribution of AQP 4 between the lateral and basal membranes.
AQP2s are regulated by VP. AQP2s sit in tiny sacs called vesicles beneath the apical membrane. When VP binds with its vasopressin-2 receptor (V2R), it stimulates the adenylyl cyclase (AdC) enzyme system via a Gs protein. AdC, in turn, instigates an elevation of cyclic adenosine monophosphate (cAMP) levels, which promotes protein kinase A (PKA). PKA induces the AQP2-bearing vesicles to travel to and fuse with the apical membrane. Once there, the AQP2s are inserted into the apical membrane, dramatically increasing the amount of water that can flow across it. When VP withdraws from the cell, the AQP2s are retrieved from the cell, taken back to the interior of the cell, and the apical membrane returns to its low level of water permeability.
Researchers are beginning to ask how the AQP2-bearing vesicles are brought to the apical membrane and how do they fuse with it. They are beginning to identify proteins present in AQP2-bearing vesicles and in the apical membrane that might play an important role in the targeting, docking and fusion of these vesicles. AQPs 3 and 4 do not seem to participate in this type of shuttling process.
This molecular sequence is how VP regulates the short-term inner medullary collecting duct (IMCD) water permeability. Under laboratory conditions, the water permeability begins to rise within 40 seconds of the exposure of the IMCD to VP. At eight minutes Pf has risen to half its maximum response. It reaches its full response within 40 - 50 minutes. When VP is withdrawn, Pf falls rapidly.
The water permeability is regulated in the long-term by a sustained increase in CD water permeability in response to prolonged antidiuresis, often reached by dehydration through water deprivation. This response requires 24 or more hours to elicit and is not rapidly reversible.