Transport of water against its concentration gradient: fact or fiction?

Abstract Water transport across cell membranes is central to most physiological functions. About 200 L of water move across epithelial cells each day in humans in order to maintain whole‐body homeostasis; water transport in and out of organs such as the brain and eye are of major clinical importance. It is well established that the water transport is driven by ion transport, but how? Osmosis is not always the answer: water can be transported against considerable osmotic gradients, apparently without any external osmotic or hydrostatic driving forces. It is generally accepted that cotransporters of the symport type play a key role for the coupling between ion and water fluxes. Models of coupling are either molecular or based on unstirred layer effects, and can be distinguished by their response time: for molecular models, water transport follows changes of substrate transport instantaneously; in unstirred layer models there is a delay while the osmolarity changes in the solutions surrounding the cotransport protein. For cotransporters expressed heterologously in Xenopus oocytes, influx of water can be detected about 1 second after initiation of cotransport of ions and other substrates. This is 20 times faster than expected (and observed) for unstirred layer effects. Water transport in cotransporters is best explained by a molecular model in which ion and water fluxes are coupled by a mechanism within the protein. This would also clarify how cotransporters exploit the free energy in the ion fluxes for the uphill transport of water. WIREs Membr Transp Signal 2012, 1:373–381. doi: 10.1002/wmts.54 For further resources related to this article, please visit the WIREs website .