Fourfold Reduction of Water Permeability in Inner Medullary Collecting Duct of Aquaporin-4 Knockout Mice
| Title: | Fourfold Reduction of Water Permeability in Inner Medullary Collecting Duct of Aquaporin-4 Knockout Mice |
|---|---|
| Authors: | Verkman, Alan S.; Knepper, Mark; Chou, Chung-Lin; Ma, Tonghui; Yang, Baoxue |
| Publisher: | American Journal of Physiology |
| Date Published: | February 01, 1998 |
| Reference Number: | 204 |
Aquaporin (AQP)-3 and AQP4 water channels are expressed at the basolateral membrane of mammalian collecting duct epithelium. To determine the contribution of AQP4 to water permeability in the initial inner medullary collecting duct (IMCD), osmotic water permeability (Pf) was compared in isolated perfused IMCD segments from wild-type and AQP4 knockout mice. The AQP4 knockout mice were previously found to have normal gross appearance, survival, growth, and kidney morphology and a mild urinary concentrating defect (T. Ma, B. Yang, A. Gillespie, E. J. Carlson, C. J. Epstein, and A. S. Verkman, J. Clin. Invest. 100: 957-962, 1997). Transepithelial Pf was measured in microdissected IMCDs after 18-48 h of water deprivation and in the presence of 0.1 nM arginine vasopressin (to make basolateral Pf rate limiting). Pf values (37 degrees C; means +/- SE in cm/s x 10(-3)) were 56.0 +/- 8.5 for wild-type mice (n = 5) and 13.1 +/- 3.7 for knockout mice (n = 6) (P < 0.001). Northern blot analysis of kidney showed that transcript expression of AQP1, AQP2, AQP3, and AQP6 were not affected by AQP4 deletion. Immunoblot analysis indicated no differences in protein expression of AQP1, AQP2, or AQP3, and immunoperoxidase showed no differences in staining patterns. Coexpression of AQP3 and AQP4 in Xenopus laevis oocytes showed additive water permeabilities, suggesting that AQP4 deletion does not affect AQP3 function. These results indicate that AQP4 is responsible for the majority of basolateral membrane water movement in IMCD but that its deletion is associated with a very mild defect in urinary concentrating ability.
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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.
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Water-transporting proteins called aquaporins (AQPs) are located within the principal cells of the CD. AQPs act as channels through which water can pass through the cell membrane. Thus, AQPs make the CD cell membranes much more water permeable than they otherwise would be.
Chou, et al., investigated the extent to which one type of AQP, AQP4, contributed to the IMCD cell membrane water permeability. To do this, they compared the water permeability rates of IMCD tissue of mice genetically engineered to have no AQP4s and normal mice. They found that the mice IMCD tissue without AQP4s had a fourfold reduction of water permeability compared to the IMCD tissue of normal mice.
The authors tested to see if the lack of AQP4 in the genetically engineered mice adversely affected the expression and function of their AQP1, AQP2, AQP3 and AQP6, also located in the CD. It did not. Therefore, the authors could be sure that the fourfold water permeability reduction in the IMCD was due to the missing AQP4. This indicates that AQP4 is responsible for the majority of water movement through the basolateral membrane of the IMCD cells.
Of interest was the observation that, while alive, the mice missing AQP4 only showed a mild urinary concentrating defect. This would indicate that sufficient amounts of water was being reabsorbed through the CD in order to produce concentrated urine. In other words, AQP4 deletion had a profound effect on water permeability in the IMCD, but only a modest effect on urinary concentrating ability.
This is because the amount of water reabsorbed through the CCD far exceeds that absorbed in the OMCD and IMCD together, and AQP4 is found mostly in the IMCD.