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Identification and functional significance of a brain aquaporin‐4/Na+, K+‐ATPase/mGluR5 macromolecular complex
Author(s) -
Borisovna Illarionova Nina,
Gunnarson Eli,
Zelenina Marina,
KamaliZare Padideh,
Brismar Hjalmar,
Bondar Alexander,
Zelenin Sergey,
Aperia Anita
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1159.17
Subject(s) - astrocyte , aquaporin 4 , chemistry , glutamate receptor , biophysics , metabotropic glutamate receptor 5 , metabotropic glutamate receptor , microbiology and biotechnology , atpase , biochemistry , receptor , biology , neuroscience , enzyme , central nervous system
The water channel aquaporin‐4 (AQP4) is expressed in astrocytes, which play a major role in clearing the narrow extracellular space (ES) between neurons and astrocyte endfeet from K + and glutamate released during neuronal activity. Compelling evidence suggests that AQP4 may play a role in the K + clearance. Here we show that AQP4 co‐immunoprecipitates with Na + , K + ‐ATPase and inwardly rectifying K + channel Kir4.1; transporters of key importance for the K + clearance. Using GST pull down assay, we identified the MVAFKGVWTQ of the AQP4 N‐terminus as the site for interaction with Na + ,K + ‐ATPase. The metabotropic glutamate receptor mGluR5 was also pulled down by AQP4. Using rubidium uptake and astrocyte water permeability measurements, we found that the mGluR agonist DHPG increased both Na + ,K + ‐ATPase‐mediated K + transport and AQP4‐mediated water transport. Finally, we created a mathematical model, of K + transport across the plasma membrane in the ES. This model predicts that AQP4‐driven water transport will facilitate K + clearance and stabilize the membrane potential. Thus we have demonstrated a multiprotein K + ‐transporting microdomain in the astrocyte that includes AQP4. This microdomain is functionally regulated by glutamate and serves to optimize the clearance of K + from the ES.