• Login
    View Item 
    •   DSpace Home
    • Nobel Prize Winners
    • Peter Agre
    • View Item
    •   DSpace Home
    • Nobel Prize Winners
    • Peter Agre
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Delayed K+ clearance associated with aquaporin-4 mislocalization: Phenotypic defects in brains of α-syntrophin-null mice

    Thumbnail
    View/Open
    PNAS-2003-Amiry-Moghaddam-13615-20.pdf (484.9Kb)
    Date
    2003-11-11
    Author
    Ottersen, O P
    Agre, P
    Froehner, S C
    Adams, M E
    Nagelhus, E A
    de Lanerolle, N C
    Eid, T
    Palomba, M
    Williamson, A
    Amiry-Moghaddam, M
    Metadata
    Show full item record
    Abstract
    Recovery from neuronal activation requires rapid clearance of potassium ions (K+) and restoration of osmotic equilibrium. The predominant water channel protein in brain, aquaporin-4 (AQP4), is concentrated in the astrocyte end-feet membranes adjacent to blood vessels in neocortex and cerebellum by association with alpha-syntrophin protein. Although AQP4 has been implicated in the pathogenesis of brain edema, its functions in normal brain physiology are uncertain. In this study, we used immunogold electron microscopy to compare hippocampus of WT and alpha-syntrophin-null mice (alpha-Syn-/-). We found that <10% of AQP4 immunogold labeling is retained in the perivascular astrocyte end-feet membranes of the alpha-Syn-/- mice, whereas labeling of the inwardly rectifying K+ channel, Kir4.1, is largely unchanged. Activity-dependent changes in K+ clearance were studied in hippocampal slices to test whether AQP4 and K+ channels work in concert to achieve isosmotic clearance of K+ after neuronal activation. Microelectrode recordings of extracellular K+ ([K+]o) from the target zones of Schaffer collaterals and perforant path were obtained after 5-, 10-, and 20-Hz orthodromic stimulations. K+ clearance was prolonged up to 2-fold in alpha-Syn-/- mice compared with WT mice. Furthermore, the intensity of hyperthermia-induced epileptic seizures was increased in approximately half of the alpha-Syn-/-mice. These studies lead us to propose that water flux through perivascular AQP4 is needed to sustain efficient removal of K+ after neuronal activation.
    URI
    http://jhir.library.jhu.edu/handle/1774.2/33883
    Collections
    • Peter Agre

    DSpace software copyright © 2002-2015  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    @mire NV
     

     

    Browse

    All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    DSpace software copyright © 2002-2015  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    @mire NV