NDLI: What do aquaporin knockout studies tell us about fluid transport in epithelia?

Content Provider	PubMed Central
Author	Maclaren, Oliver J. Sneyd, James Crampin, Edmund J.
Abstract	The investigation of near-isosmotic water transport in epithelia goes back over 100 years; however debates over mechanism and pathway still remain. Aquaporin (AQP) knockouts have been used by various research groups to test the hypothesis of an osmotic mechanism, as well as to explore the paracellular vs transcellular pathway debate. Non-proportional reductions in the water permeability of a water-transporting epithelial cell (e.g. a reduction of around 80–90%) compared to the reduction in overall water transport rate in the knockout animal (e.g. a reduction of 50–60%) are commonly found. This non-proportionality has led to controversy over whether AQP knockout studies support or contradict the osmotic mechanism. Arguments raised for and against an interpretation supporting the osmotic mechanism typically have partially-specified, implicit or incorrect assumptions. We present a simple mathematical model of the osmotic mechanism with clear assumptions and, for models based on this mechanism, establish a baseline prediction of AQP knockout studies. We allow for deviations from isotonic/isosmotic conditions and utilize dimensional analysis to reduce the number of parameters that must be considered independently. This enables a single prediction curve to be used for multiple epithelial systems. We find that a simple, transcellular-only osmotic mechanism sufficiently predicts the results of knockout studies and find criticisms of this mechanism to be overstated. We note, however, that AQP knockout studies do not give sufficient information to definitively rule out an additional paracellular pathway.
Related Links	http://dx.doi.org/10.1007/s00232-013-9530-2
Ending Page	305
Page Count	9
Starting Page	297
File Format	PDF
ISSN	00222631
e-ISSN	14321424
Journal	The Journal of membrane biology
Issue Number	4
Volume Number	246
Language	English
Publisher Date	2013-04-01
Access Restriction	Open
Subject Keyword	Biophysics Cell Biology Physiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology Biophysics

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