Send to

Choose Destination
J Biol Chem. 2016 Sep 2;291(36):19184-95. doi: 10.1074/jbc.M116.740217. Epub 2016 Jul 19.

Aquaporin 4 as a NH3 Channel.

Author information

From the Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany, and.
Division of General Zoology, Department of Biology, University of Kaiserslautern, 67653 Kaiserslautern, Germany.
From the Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark,


Ammonia is a biologically potent molecule, and the regulation of ammonia levels in the mammalian body is, therefore, strictly controlled. The molecular paths of ammonia permeation across plasma membranes remain ill-defined, but the structural similarity of water and NH3 has pointed to the aquaporins as putative NH3-permeable pores. Accordingly, a range of aquaporins from mammals, plants, fungi, and protozoans demonstrates ammonia permeability. Aquaporin 4 (AQP4) is highly expressed at perivascular glia end-feet in the mammalian brain and may, with this prominent localization at the blood-brain-interface, participate in the exchange of ammonia, which is required to sustain the glutamate-glutamine cycle. Here we observe that AQP4-expressing Xenopus oocytes display a reflection coefficient <1 for NH4Cl at pH 8.0, at which pH an increased amount of the ammonia occurs in the form of NH3 Taken together with an NH4Cl-mediated intracellular alkalization (or lesser acidification) of AQP4-expressing oocytes, these data suggest that NH3 is able to permeate the pore of AQP4. Exposure to NH4Cl increased the membrane currents to a similar extent in uninjected oocytes and in oocytes expressing AQP4, indicating that the ionic NH4 (+) did not permeate AQP4. Molecular dynamics simulations revealed partial pore permeation events of NH3 but not of NH4 (+) and a reduced energy barrier for NH3 permeation through AQP4 compared with that of a cholesterol-containing lipid bilayer, suggesting AQP4 as a favored transmembrane route for NH3 Our data propose that AQP4 belongs to the growing list of NH3-permeable water channels.


ammonia; aquaporin 4 (AQP4); membrane protein; molecular dynamics; permeability

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center