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

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dc.contributor.author Ottersen, O P
dc.contributor.author Agre, P
dc.contributor.author Froehner, S C
dc.contributor.author Adams, M E
dc.contributor.author Nagelhus, E A
dc.contributor.author de Lanerolle, N C
dc.contributor.author Eid, T
dc.contributor.author Palomba, M
dc.contributor.author Williamson, A
dc.contributor.author Amiry-Moghaddam, M
dc.date.accessioned 2010-03-04T19:42:08Z
dc.date.available 2010-03-04T19:42:08Z
dc.date.issued 2003-11-11
dc.identifier.citation Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13615-20. Epub 2003 Nov 3. http://www.pnas.org/content/100/23/13615.full en
dc.identifier.uri http://jhir.library.jhu.edu/handle/1774.2/33883
dc.description.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. en
dc.description.provenance Submitted by Janice Chen (janice.chen@jhu.edu) on 2010-03-04T17:29:53Z No. of bitstreams: 1 PNAS-2003-Amiry-Moghaddam-13615-20.pdf: 496561 bytes, checksum: a1df7cee4727e40d2202104fc9b4e404 (MD5) en
dc.description.provenance Approved for entry into archive by David Reynolds(davidr@jhu.edu) on 2010-03-04T19:42:08Z (GMT) No. of bitstreams: 1 PNAS-2003-Amiry-Moghaddam-13615-20.pdf: 496561 bytes, checksum: a1df7cee4727e40d2202104fc9b4e404 (MD5) en
dc.description.provenance Made available in DSpace on 2010-03-04T19:42:08Z (GMT). No. of bitstreams: 1 PNAS-2003-Amiry-Moghaddam-13615-20.pdf: 496561 bytes, checksum: a1df7cee4727e40d2202104fc9b4e404 (MD5) Previous issue date: 2003-11-11 en
dc.language.iso en_US en
dc.publisher National Academy of Sciences en
dc.subject Potassium/metabolism en
dc.subject Muscle Proteins/physiology en
dc.subject Membrane Proteins/physiology en
dc.subject Brain/metabolism en
dc.title Delayed K+ clearance associated with aquaporin-4 mislocalization: Phenotypic defects in brains of α-syntrophin-null mice en
dc.type Article en

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