Sodium channel activity modulates multiple functions in microglia

Joel A. Black; Shujun Liu; Stephen G. Waxman

doi:10.1002/glia.20830

journal article Dec 29, 2008

Sodium channel activity modulates multiple functions in microglia

Joel A. Black Shujun Liu

Stephen G. Waxman

Glia Vol. 57 No. 10 pp. 1072-1081 · Wiley

View at Publisher Save 10.1002/glia.20830

Abstract

AbstractMicroglia provide surveillance in the central nervous system and become activated following tissue insult. Detailed mechanisms by which microglia detect and respond to their environment are not fully understood, but it is known that microglia express a number of surface receptors and ion channels, including voltage‐gated sodium channels, that participate in transduction of external stimuli to intra‐cellular responses. To determine whether activated microglia are affected by the activity of sodium channels, we examined the expression of sodium channel isoforms in cultured microglia and the action of sodium channel blockade on multiple functions of activated microglia. Rat microgliain vitroexpress tetrodotoxin (TTX)‐sensitive sodium channels Nav1.1 and Nav1.6 and the TTX‐resistant channel Nav1.5, but not detectable levels of Nav1.2, Nav1.3, Nav1.7, Nav1.8, and Nav1.9. Sodium channel blockade with phenytoin (40 μM) and TTX (0.3 μM) significantly reduced by 50–60% the phagocytic activity of microglia activated with lipopolysaccharide (LPS); blockade with 10 μM TTX did not further reduce phagocytic activity. Phenytoin attenuated by ∼50% the release of IL‐1α, IL‐1β, and TNF‐α from LPS‐stimulated microglia, but had minimal effects on the release of IL‐2, IL‐4, IL‐6, IL‐10, MCP‐1, and TGF‐α. TTX (0.3 μM) reduced, but to a smaller extent, the release of IL‐1α, IL‐1β, and TNF‐α from activated microglia. Phenytoin and TTX also significantly decreased by ∼50% adenosine triphosphate‐induced migration by microglia; studies with microglia cultured frommedmice (which lack Nav1.6) indicate that Nav1.6 plays a role in microglial migration. The results demonstrate that the activity of sodium channels contributes to effector roles of activated microglia. © 2008 Wiley‐Liss, Inc.

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Details

Published: Dec 29, 2008
Vol/Issue: 57(10)
Pages: 1072-1081
License: View

Authors

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom; Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut; and Rehabilitation Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut

Cite This Article

Joel A. Black, Shujun Liu, Stephen G. Waxman (2008). Sodium channel activity modulates multiple functions in microglia. Glia, 57(10), 1072-1081. https://doi.org/10.1002/glia.20830

Sodium channel activity modulates multiple functions in microglia

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