Curtin University Homepage
  • Library
  • Help
    • Admin

    espace - Curtin’s institutional repository

    JavaScript is disabled for your browser. Some features of this site may not work without it.
    View Item 
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item
    • espace Home
    • espace
    • Curtin Research Publications
    • View Item

    Specific combinations of ion channel inhibitors reduce excessive Ca2+ influx as a consequence of oxidative stress and increase neuronal and glial cell viability in vitro

    257923.pdf (509.7Kb)
    Access Status
    Open access
    Authors
    O'Hare Doig, R.
    Bartlett, C.
    Smith, N.
    Hodgetts, S.
    Dunlop, S.
    Hool, L.
    Fitzgerald, Melinda
    Date
    2016
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    O'Hare Doig, R. and Bartlett, C. and Smith, N. and Hodgetts, S. and Dunlop, S. and Hool, L. and Fitzgerald, M. 2016. Specific combinations of ion channel inhibitors reduce excessive Ca2+ influx as a consequence of oxidative stress and increase neuronal and glial cell viability in vitro. Neuroscience. 339: pp. 450-462.
    Source Title
    Neuroscience
    DOI
    10.1016/j.neuroscience.2016.10.005
    ISSN
    0306-4522
    School
    Health Sciences Research and Graduate Studies
    URI
    http://hdl.handle.net/20.500.11937/59506
    Collection
    • Curtin Research Publications
    Abstract

    Combinations of Ca 2+ channel inhibitors have been proposed as an effective means to prevent excess Ca 2+ flux and death of neurons and glia following neurotrauma in vivo. However, it is not yet known if beneficial outcomes such as improved viability have been due to direct effects on intracellular Ca 2+ concentrations. Here, the effects of combinations of Lomerizine (Lom), 2,3-dioxo-7-(1H-imidazol-1-yl)6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]acetic acid monohydrate (YM872), 3,5-dimethyl-1-adamantanamine (memantine (Mem)) and/or adenosine 5'-triphosphate periodate oxidized sodium salt (oxATP) to block voltage-gated Ca 2+ channels, Ca 2+ permeable a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, NMDA receptors and purinergic P2X 7 receptors (P2X 7 R) respectively, on Ca 2+ concentration and viability of rat primary mixed cortical (MC) cultures exposed to hydrogen peroxide (H 2 O 2 ) insult, were assessed. The contribution of ryanodine-sensitive intracellular stores to intracellular Ca 2+ concentration was also assessed. Live cell calcium imaging revealed that a 30 min H 2 O 2 insult induced a slow increase in intracellular Ca 2+ , in part from intracellular sources, associated with loss of cell viability by 6 h. Most combinations of inhibitors that included oxATP significantly decreased Ca 2+ influx and increased cell viability when administered simultaneously with H 2 O 2 . However, reductions in intracellular Ca 2+ concentration were not always linked to improved cell viability. Examination of the density of specific cell subpopulations demonstrated that most combinations of inhibitors that included oxATP preserved NG2+ non-oligodendroglial cells, but preservation of astrocytes and neurons required additional inhibitors. Olig2 + oligodendroglia and ED-1 + activated microglia/macrophages were not preserved by any of the inhibitor combinations. These data indicate that following H 2 O 2 insult, limiting intracellular Ca 2+ entry via P2X 7 R is generally associated with increased cell viability. Protection of NG2+ non-oligodendroglial cells by Ca 2+ channel inhibitor combinations may contribute to observed beneficial outcomes in vivo.

    Related items

    Showing items related by title, author, creator and subject.

    • Novel strategies for inhibiting cancer growth
      Schaefer, Rainer (2008)
      At present, most cancers are treated with surgery, radiotherapy and chemotherapy, used alone or in combination. Surgery and radiotherapy are the primary treatment modalities after early detection of cancers and they ...
    • Lysosomal cystine accumulation promotes mitochondrial depolarization and induction of redox-sensitive genes in human kidney proximal tubular cells
      Sumayao, R.; McEvoy, B.; Newsholme, Philip; McMorrow, T. (2016)
      Key points: Cystine is a disulphide amino acid that is normally generated in the lysosomes by the breakdown of cystine-containing proteins. Previously, we demonstrated that lysosomal cystine accumulation in kidney proximal ...
    • Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma
      O'Hare Doig, R.; Chiha, W.; Giacci, M.; Yates, N.; Bartlett, C.; Smith, N.; Hodgetts, S.; Harvey, A.; Fitzgerald, Melinda (2017)
      Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux ...
    Advanced search

    Browse

    Communities & CollectionsIssue DateAuthorTitleSubjectDocument TypeThis CollectionIssue DateAuthorTitleSubjectDocument Type

    My Account

    Admin

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    Follow Curtin

    • 
    • 
    • 
    • 
    • 

    CRICOS Provider Code: 00301JABN: 99 143 842 569TEQSA: PRV12158

    Copyright | Disclaimer | Privacy statement | Accessibility

    Curtin would like to pay respect to the Aboriginal and Torres Strait Islander members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Whadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.