Mechanisms and Regulation of Water Permeability in Renal Epithelia

Title: Mechanisms and Regulation of Water Permeability in Renal Epithelia
Author: Verkman, Alan S.
Publisher: American Journal of Physiology
Date Published: November 01, 1989
Reference Number: 214
Water transport occurs in all biological membranes. A few selected membranes in the kidney, amphibian urinary bladder, and erythrocyte have very high water permeability and are thought to contain specialized water transporting units termed "water channels." The known biophysical properties of membranes containing water channels are a high osmotic water permeability coefficient (Pf), an osmotic-to-diffusional water permeability coefficient ratio (Pf/Pd) greater than unity, a low activation energy (Ea), and inhibition by mercurial compounds. The biochemical and molecular characteristics of water channel pathways are not known at present. Established and new methods to measure Pf and Pd in kidney tubules and in isolated membrane vesicles from kidney cells are reviewed and evaluated. In the mammalian proximal tubule, a high Pf results from transcellular movement of water across highly permeable apical and basolateral membranes containing water channels. It has been assumed that proximal tubule Pf is unregulated; however, recent results indicate that apical water channels are retrieved by endocytosis and that Pf is decreased fivefold with increasing transepithelial osmotic gradients. In the thin and thick ascending limbs, Pf is nearly the lowest of all biological membranes and is not subject to regulation. In contrast, collecting tubule Pf is subject to hormonal regulation by vasopressin. Vasopressin binding to receptors located at the basal membrane of principal cells initiates adenosine 3',5'-cyclic monophosphate production, which is thought ultimately to activate the exocytic insertion of intracellular vesicles containing water channels into the cell apical membrane. Vasopressin-induced endosomes from kidney collecting tubule and toad urinary bladder contain functional water channels but no proton pumps or urea transporters, supporting a membrane shuttle hypothesis that is selective for water channels. Future directions for the isolation and molecular cloning of kidney water channels are evaluated.

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)

Water movement across cell membranes is an essential requirement for body water balance, and body water balance is essential to health. Whereas most cell plasma membranes require only that water diffuse through them, some require that water transport across them much more rapidly and in greater volume than is possible through diffusion alone. Examples of the latter type of cell membrane are found in the human red blood cell, and the cells of certain sections of the kidney. These cell membranes are thought to contain water channels: proteins that insert themselves into the membranes to form channels through which water can pass with relatively great speed and volume.

Water transport across cell membranes is difficult to measure so there is still much that is unknown about water transport mechanisms. Researchers have devised a number of measuring methods, some of which disrupt the function of the tissues they are measuring more than others. Still, the differing methods have found enough results in common to provide a solid framework for beginning to understand how and by what processes water transports across different cell membranes, the rate and volume at which it does in each place, and some of the biochemical and molecular variables, parameters and structures involved in the transport.

For example, membranes that contain water channels are known to have the following biophysical properties:

  1. A relatively large amount of water flows through them rapidly. This is called having a high osmotic water permeability coefficient (Pf)
  2. More water crosses the membranes through osmotic permeability than through diffusing across the membranes.
  3. It requires a low activation energy (Ea) to set the water transport in motion.
  4. Water transport across the membranes is inhibited in the presence of mercurial compounds.

The kidney is an ideal organ in which to study water transport across cell membranes because water transports across membranes there by various processes -- diffusion, osmosis, with the aid of water channels and without water channels -- depending on what part of the kidney is being examined. In one section of the kidney called the tubule both diffusional and osmotic water permeability take place. The tubule is separated into different segments. The segment closest to a filter called the glomerulus is called the proximal tubule. The segment furthest from the glomerulus is called the distal tubule. The segment in-between the proximal and distal tubule is called the limb of Henle. It has two ascending limbs and two descending limbs. The distal tubule empties into the collecting duct.

The thin descending limb of Henle is highly water permeable, whereas the thin and thick ascending limbs have extremely low water permeability. The proximal tubule has a high degree of water permeability and contains water channels. The collecting duct principal cell membranes are impermeable at the apex and permeable at the base and sides. The different degrees of permeability of the tubule are essential for the body water that flows through it to be reabsorbed into the inner tissues of the kidney.

Water channels are either regulated constitutively or by hormonal signals. It was thought that the proximal tubule water channels were constitutively regulated, which means they were not regulated (activated or deactivated) by a hormone. Instead it was thought they performed their function constantly in a fixed manner, regardless of conditions external to the cell membrane. Recent studies indicate that their function may be regulated.

The principal cells of the kidney collecting duct have water channels in both their basolateral and apical membranes. The apical membrane is normally water impermeable, but becomes highly permeable when water channels insert themselves into it. These channels are regulated by a hormone. That is, they perform their water transporting function only when signaled to do so by a specific hormone.

These water channels reside in little sacs called vesicles. The vesicles rest inside the cell just beneath the apical membrane. When they are signaled by a molecular sequence initiated by the hormone, vasopressin (VP), they shuttle to the apical cell membrane and fuse with it. Then the water channels inside the vesicle insert themselves into the apical membrane and the membrane goes from being water impermeable to being highly water permeable. This allows the body water flowing through the collecting duct to be reabsorbed by the inner tissues of the kidney.

When VP removes itself from the collecting duct cells, it is thought the embedded water channels remove themselves from the apical membrane and are taken inside the vesicles back to their holding place inside the cells. Whereas many other protein-bearing vesicles acidify and dissolve at this point, researchers think that these water channel-bearing vesicles do not undergo this process and instead wait until once again signaled by VP to cycle back to the apical membrane. This notion of the cyclic movement of the water channel-bearing vesicles is called the shuttle hypothesis.

There is speculation that VP, in addition to making the apical membrane more water permeable by signaling the water channels to insert themselves in it, actually increases the membrane fluidity of the apical membrane itself. If this is so, the increased membrane fluidity would increase the membrane's water permeability. If further tests reveal that there is a significant alteration in apical membrane fluidity by VP, then it will be necessary to establish the mechanism by which fluidity is altered along with the role of apical membrane fluidity in the hydrosmotic response.

To understand more about water channel pathways, future research must label, isolate and reconstitute water transporters. Ultimately, the molecular cloning of water transporting units, together with structural and biophysical studies, will be required to understand how water moves across biological membranes.