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

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 Na_v1.5 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 Na_v1.5 mRNA knockdown. Our results suggest that Na_v1.5 and NCX are potential targets for modulation of astrogliosis after injury via their effect on Ca²⁺]_i. GLIA 2014;62:1162–1175