Format

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

1
From the Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark.
2
Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, 37077 Gottingen, Germany, and.
3
Division of General Zoology, Department of Biology, University of Kaiserslautern, 67653 Kaiserslautern, Germany.
4
From the Department of Neuroscience and Pharmacology, University of Copenhagen, 2200 Copenhagen, Denmark, macaulay@sund.ku.dk.

Abstract

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.

KEYWORDS:

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

PMID:
27435677
PMCID:
PMC5009286
DOI:
10.1074/jbc.M116.740217
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

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