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Voltage‐gated sodium channel Na v 1.5 contributes to astrogliosis in an in vitro model of glial injury via reverse Na + /Ca 2+ exchange
Author(s) -
Pappalardo Laura W.,
Samad Omar A.,
Black Joel A.,
Waxman Stephen G.
Publication year - 2014
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22671
Subject(s) - astrogliosis , astrocyte , gene knockdown , glial scar , neuroglia , sodium channel , gliosis , biology , neuroscience , sodium calcium exchanger , microbiology and biotechnology , biophysics , sodium , chemistry , central nervous system , cell culture , intracellular , organic chemistry , genetics
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 + /Ca 2+ exchanger (NCX), and by knockdown of Na v 1.5 mRNA. We also show that astrocytes display a robust [Ca 2+ ] i transient after mechanical injury and demonstrate that this [Ca 2+ ] i response is also attenuated by TTX, KB‐R7943, and Na v 1.5 mRNA knockdown. Our results suggest that Na v 1.5 and NCX are potential targets for modulation of astrogliosis after injury via their effect on [Ca 2+ ] i . GLIA 2014;62:1162–1175