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      Neural Dysfunction and Neurodegeneration in Drosophila Na +/K + ATPase Alpha Subunit Mutants

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          Abstract

          The Na +/K + ATPase asymmetrically distributes sodium and potassium ions across the plasma membrane to generate and maintain the membrane potential in many cell types. Although these pumps have been hypothesized to be involved in various human neurological disorders, including seizures and neurodegeneration, direct genetic evidence has been lacking. Here, we describe novel mutations in the Drosophila gene encoding the α (catalytic) subunit of the Na +/K + ATPase that lead to behavioral abnormalities, reduced life span, and severe neuronal hyperexcitability. These phenotypes parallel the occurrence of extensive, age-dependent neurodegeneration. We have also discovered that the ATPalpha transcripts undergo alternative splicing that substantially increases the diversity of potential proteins. Our data show that maintenance of neuronal viability is dependent on normal sodium pump activity and establish Drosophila as a useful model for investigating the role of the pump in human neurodegenerative and seizure disorders.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 February 2003
          : 23
          : 4
          : 1276-1286
          Affiliations
          [ 1 ]Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706
          Article
          PMC6742270 PMC6742270 6742270 7306
          10.1523/JNEUROSCI.23-04-01276.2003
          6742270
          12598616
          36efaf32-83d4-4d1b-8e94-a597eee78e80
          Copyright © 2003 Society for Neuroscience
          History
          : 25 September 2002
          : 27 November 2002
          : 30 November 2002
          Categories
          ARTICLE
          Cellular/Molecular
          Custom metadata
          5.00

          hyperexcitability , Na/K ATPase , paralysis , neuropathology , ATPalpha , alternative splicing , neurodegeneration , excitotoxicity

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