What Do Aquaporin Knockout Studies Tell Us about Fluid Transport in Epithelia?
- 427 Downloads
The investigation of near-isosmotic water transport in epithelia goes back over 100 years; however, debates over mechanism and pathway 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 versus transcellular pathway debate. Nonproportional 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 nonproportionality 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.
KeywordsAquaporin knockout Epithelial transport Osmosis Aquaporins Water transport Osmotic mechanism
O. J. M. was supported by the New Zealand Tertiary Education Commission’s Top Achiever Doctoral Scholarship. This work was supported by NIH Grant R01 DE19245-01.
- Finkelstein A (1987) Water movement through lipid bilayers, pores, and plasma membranes: theory and reality, vol 4. Wiley, New YorkGoogle Scholar
- Logan D (1997) Applied mathematics. Wiley, New YorkGoogle Scholar
- Reuss L (2009) Water transport by epithelia. Wiley, HobokenGoogle Scholar
- Reuss L (2010) Epithelial transport. Wiley, HobokenGoogle Scholar
- Weinstein A, Stephenson J, Spring K (1981) The coupled transport of water. In: Bonting SL, de Pont JJHHM (eds) New comprehensive biochemistry. Membrane transport. Elsevier, Amsterdam, pp 311–351Google Scholar
- Whittembury G, Reuss L (1992) Mechanisms of coupling of solute and solvent transport in epithelia. Raven Press, New YorkGoogle Scholar