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Astrocytes within multiple sclerosis lesions upregulate sodium channel Nav1.5.

Astrocytes are prominent participants in the response of the central nervous system to injury, including neuroinflammatory insults. Rodent astrocytes in vitro have been shown to express voltage-gated sodium channels in a dynamic manner, with a switch in expression of tetrodotoxin-sensitive to tetrodotoxin-resistant channels in reactive astrocytes. However, the expression of sodium channels in human astrocytes has not been studied, and it is not known whether there are changes in the expression of sodium channels in reactive astrocytes of the human central nervous system. Here, we demonstrate a focal and robust upregulation of sodium channel Nav1.5 in reactive astrocytes at the borders of, and within, active and chronic multiple sclerosis lesions. Nav1.5 was only detectable at very low levels in astrocytes within multiple sclerosis macroscopically normal-appearing white matter or in normal control brain. Nav1.1, Nav1.2, Nav1.3 and Nav1.6 showed little or no expression in astrocytes within normal control tissue and limited upregulation in active multiple sclerosis lesions. Nav1.5 was also expressed at high levels in astrocytes in tissue surrounding new and old cerebrovascular accidents and brain tumours. These results demonstrate the expression of Nav1.5 in human astrocytes and show that Nav1.5 expression is dynamic in these cells. Our observations suggest that the upregulated expression of Nav1.5 in astrocytes may provide a compensatory mechanism, which supports sodium/potassium pump-dependent ionic homoeostasis in areas of central nervous system injury.

Pubmed ID: 20147455


  • Black JA
  • Newcombe J
  • Waxman SG


Brain : a journal of neurology

Publication Data

March 22, 2010

Associated Grants


Mesh Terms

  • Acute Disease
  • Adult
  • Aged
  • Astrocytes
  • Brain
  • Brain Neoplasms
  • Chronic Disease
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive
  • Muscle Proteins
  • NAV1.1 Voltage-Gated Sodium Channel
  • NAV1.2 Voltage-Gated Sodium Channel
  • NAV1.3 Voltage-Gated Sodium Channel
  • NAV1.5 Voltage-Gated Sodium Channel
  • NAV1.6 Voltage-Gated Sodium Channel
  • Nerve Fibers, Myelinated
  • Nerve Tissue Proteins
  • Sodium Channels
  • Stroke
  • Up-Regulation