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Updated: Aug 3, 2026

A Proteoliposome-Based Efflux Assay to Determine Single-molecule Properties of Cl- Channels and Transporters
Published on: April 20, 2015
Cotransporters as molecular water pumps
Thomas Zeuthen1, Nanna MacAulay
1Institute of Medical Physiology, The Panum Institute, University of Copenhagen, Denmark.
Molecular water pumps facilitate uphill water transport by coupling it to substrate fluxes. This cotransport mechanism is independent of external water potential, as demonstrated in electrogenic cotransporter studies.
Area of Science:
- Biochemistry
- Molecular Biology
- Membrane Transport
Background:
- Molecular water pumps are membrane proteins that couple water flux to substrate transport.
- Free energy exchange between fluxes allows water movement independent of external water potential, potentially uphill.
- This cotransport mechanism is crucial for understanding cellular water homeostasis.
Purpose of the Study:
- To review evidence for water cotransport mediated by molecular water pumps.
- To emphasize the role of electrogenic cotransporters in Xenopus oocytes under voltage clamp.
- To discuss phenomena supporting uphill water transport and tight coupling.
Main Methods:
- Review of experimental data on electrogenic cotransporters, particularly Na+/glutamate and Na+/glucose cotransporters.
- Voltage-clamped Xenopus oocyte expression system.
- Analysis of phenomena like uphill water transport, substrate cotransport, and reversal potential shifts.
Main Results:
- Evidence supports water cotransport, where water flux is tightly coupled to substrate flux and membrane current.
- Uphill water transport and cotransport of small hydrophilic molecules were observed.
- Alternative explanations like unstirred layers and electrode artifacts were experimentally and theoretically ruled out.
Conclusions:
- Molecular water pumps actively cotransport water, a process not solely driven by water chemical potential.
- The cotransport mechanism is distinct from channel or ionophore-mediated transport, generating significantly larger water fluxes.
- Theoretical models confirm minimal unstirred layer effects, supporting the cotransport hypothesis.
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