Water Channels
| Title: | Water Channels |
|---|---|
| Authors: | Harris, H. William; Zeidel, Mark L. |
| Publisher: | Current Opinion in Nephrology and Hypertension |
| Date Published: | September 01, 1993 |
| Reference Number: | 269 |
The movement of water across cell membranes has been an active area of research for more than 100 years and is of fundamental importance in the normal water metabolism of all terrestrial animals. The objective of this review is to integrate recent data obtained from the isolation and molecular cloning of water channel proteins, with functional information provided by biophysical measurements of membrane water transport. Whereas the water permeability of most cell membranes can be accounted for by the diffusion of water across the lipid bilayer, other cells, including the erythrocyte as well as certain cells in renal epithelia, possess specialized water channels. Water channels are composed of specialized proteins that create highly selective aqueous pores across cell membranes. Data concerning the distribution, permeability, and function of these various water channels will greatly enhance our knowledge of how water is transported across cell membranes.
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)
Researchers investigating these matters proposed the existence of water channels (WCs): water transporting proteins within cell membranes through which water could flow rapidly. Cells whose water movement indicated the presence of WCs include red blood cells and cells in parts of the kidney called the cortical collecting duct and the Loop of Henle. Thus, the amount of water that can cross a cell membrane is determined by how much water the lipid bilayer that comprises the cell membrane lets through and how much water the WC lets through, if it is present in the cell membrane. In their paper, Harris and Zeidel review information regarding the structure and function of water channels, especially as they exist in the red blood cells and kidney.
In the kidney, the apical cell membrane is the primary impediment to water flow. (If you imagine the cell as an upright rectangle, the segment of the membrane making up the base and sides of the rectangle is called the basolateral membrane. The membrane segment comprising the top of the rectangle is the apical membrane.) The fact that so little water can flow through the apical membrane serves a function, but in order to help balance body water it cannot always stay so impermeable, and that is where WCs come in.
When the antidiuretic hormone (ADH) binds with its receptor on the basolateral membrane of the principal cells of the kidney collecting duct, it transmits a signal which induces little sacs called water channel vesicles (WCVs) to travel to and fuse with the apical membrane. The WCVs contain WCs which insert themselves into the apical membrane, vastly increasing the amount of water that can flow through it. When ADH absents itself from the cell, the WCVs withdraw, taking the WCs with them, and are cycled back inside the cell.
This is an example of a WC that is regulated by a hormone. That is, the WC does not always reside in the apical membrane, but only inserts itself there when signaled to do so by ADH. There is another type of WC that is present continuously in the cell membrane. This category of WC is not regulated by a hormone, but resides permanently in the cell membrane and is always functioning to give the cell membrane it is in a heightened degree of water permeability so body water can move easily and quickly across it. This type of WC is present in human red blood cells, and parts of the kidney called the proximal tubule and the descending limb of the Loop of Henle. Differences between the two categories include their mechanisms of delivery to the plasma membrane and the molecular structures of the WCs themselves.
Researchers knew the biophysical properties of WCs; now they wanted to understand their molecular structure. In 1988, Denker, et al., identified the WC found in the red blood cells. It was first called CHIP-28 as it is 28 kilodaltons in size. It is now named aquaporin CHIP and researchers have deduced its structure to be as follows: Think of it as a beaded string. The beads are the amino acids that comprise the aquaporin. Most of the string lies coiled inside the cell membrane in six distinct clumps called transmembrane domains 1 - 6. Part of it snakes outside the membrane into the extracellular environment to form three curves called extracellular loops A, C, and E. Part of it snakes inside the cell to form two curves called intracellular loops B and D. Both ends of the protein, the amino terminus and the carboxy terminus, lie inside the cell with the intracellular loops. (You can look at a diagram of an aquaporin here.)
Aquaporin CHIP is a type of WC that is not regulated by a hormone. Finding the molecular structure of hormone-regulated WCs was challenging because the WCVs in which they reside contain many protein segments, some of which sort, fuse and move the WCV, and some of which are components of the WC. In the purified toad urinary bladder, WCVs contain 12 to 15 protein bands, two of which have been identified as being associated with the WC itself. One of these is 55 kilodaltons and the other is 53 kilodaltons.
Researchers studied granular cells of the toad urinary bladder to determine the fate of the WCVs and the WCs they contained. Using a fluid phase marker to stain the WCVs when they were in the apical membrane, researchers could follow the WCVs path over time back inside the cell. They found there were three distinct intracellular compartments that the fluid phase marked WCVs pass through. First, tubular endosomes, then early multivesicular body endosomes and finally late multivesicular body endosomes. (An endosome is a vesicle that has lost its coat of the protein clathrin after it has returned from the cell surface.) In the first two stages, the endosomes still contain protein-membrane particles associated with WCs and WCVs, and they still exhibit functional WCs. The last stage lacks the membrane particles and large numbers of functional WCs.
Research into water channels is ongoing and includes research designed to determine the exact structural and genetic relationships between the ADH WC and the aquaporin CHIP WC; the protein compositions of these WCs; the distribution and function of WCs in various tissues; the molecular arrangements that permit apical membranes of certain cells to have an extremely low level of water permeability; and the WCV proteins that control vesicle fusion and removal from the apical membrane.