Get access

Voltage-gated sodium channel Nav1.5 contributes to astrogliosis in an in vitro model of glial injury via reverse Na+/Ca2+ exchange

Authors

  • Laura W. Pappalardo,

    1. Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut
    2. Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, Connecticut
    Search for more papers by this author
    • Laura W. Pappalardo and Omar A. Samad contributed equally to this work.

  • Omar A. Samad,

    1. Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut
    2. Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, Connecticut
    Search for more papers by this author
    • Laura W. Pappalardo and Omar A. Samad contributed equally to this work.

  • Joel A. Black,

    1. Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut
    2. Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, Connecticut
    Search for more papers by this author
  • Stephen G. Waxman

    Corresponding author
    1. Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut
    2. Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, Connecticut
    • Address correspondence to Stephen G. Waxman, MD, PhD, Neuroscience and Regeneration Research Center VA Connecticut Healthcare System, 950 Campbell Avenue, Bldg. 34 West Haven, CT 06516, USA. E-mail: stephen.waxman@yale.edu

    Search for more papers by this author

Abstract

Astrogliosis is a prominent feature of many, if not all, pathologies of the brain and spinal cord, yet a detailed understanding of the underlying molecular pathways involved in the transformation from quiescent to reactive astrocyte remains elusive. We investigated the contribution of voltage-gated sodium channels to astrogliosis in an in vitro model of mechanical injury to astrocytes. Previous studies have shown that a scratch injury to astrocytes invokes dual mechanisms of migration and proliferation in these cells. Our results demonstrate that wound closure after mechanical injury, involving both migration and proliferation, is attenuated by pharmacological treatment with tetrodotoxin (TTX) and KB-R7943, at a dose that blocks reverse mode of the Na+/Ca2+ exchanger (NCX), and by knockdown of Nav1.5 mRNA. We also show that astrocytes display a robust [Ca2+]i transient after mechanical injury and demonstrate that this [Ca2+]i response is also attenuated by TTX, KB-R7943, and Nav1.5 mRNA knockdown. Our results suggest that Nav1.5 and NCX are potential targets for modulation of astrogliosis after injury via their effect on [Ca2+]i. GLIA 2014;62:1162–1175

Ancillary