Cotransporters as molecular water pumps.

Molecular water pumps are membrane proteins of the cotransport type in which a flux of water is coupled to substrate fluxes by a mechanism within the protein. Free energy can be exchanged between the fluxes. Accordingly, the flux of water may be relatively independent of the external water chemical potential and can even proceed uphill. In short, water is being cotransported. The evidence for water cotransport is reviewed with particular emphasis on electrogenic cotransporters expressed in Xenopus oocytes under voltage clamped conditions. Phenomena such as uphill water transport, tight coupling between water transport and clamp current, cotransport of small hydrophilic molecules, and shifts in reversal potentials with osmolarity are discussed with examples from the Na+/glutamate and Na+/glucose cotransporters. Unstirred layers and electrode artifacts as alternative explanations for such cotransport can be ruled out for both experimental and theoretical reasons. Indeed, substrate fluxes mediated by channels or ionophores generate much smaller water fluxes than those observed with cotransporters. Theoretical models, using reasonable values for the intracellular diffusion coefficient, indicate the presence of only small unstirred layers in the membranes studied.