, 1989). The expression of sodium channels in OPCs may have important physiological consequences. It is known that action potential activity can lead to vesicular glutamate release at discrete sites along axons, and this can activate ionotropic glutamate receptors on neighboring OPCs (Kukley et al., 2007). Eighty-one percent of OPCs

that express sodium channels respond to this type of neurotransmitter release, whereas only 2% of OPCs that lack sodium channel expression show these responses, suggesting that the ability selleck chemical of OPCs to respond to axonal signaling may be associated with the expression of sodium channels within these cells (Káradóttir et al., 2008). In fact, it has been hypothesized that the activity of these channels may trigger myelination by these cells (Káradóttir et al., 2008). One possible mechanism is that expression of sodium channels in OPCs participates in setting their resting membrane potential, and this, in turn, may contribute to controlling their rate of proliferation (Xie et al., 2007). Switches in sodium current expression are not confined to healthy nonexcitable cells but have also been reported after pathological challenge. For example, in an in vitro model of astrogliosis in which a confluent layer of cultured rat astrocytes was scratched for the production of a linear injury, the injury evoked a switch from TTX-S

currents to TTX-R sodium currents (MacFarlane and Sontheimer, 1998). Consistent with the change in sodium currents, markedly upregulated expression of the TTX-R sodium channel, Nav1.5, was recently reported in reactive Palbociclib solubility dmso astrocytes at the boundary of the scar injury in this in vitro model (Samad et al., 2013). Importantly, upregulation of sodium channels in reactive astrocytes occurs in situ within the human brain. Observations on rapid-autopsy tissues

demonstrate robust upregulation of Nav1.5, which is not seen in normal control brains, within scarring astrocytes in acute and chronic MS plaques and adjacent to cerebrovascular accidents and neoplastic oxyclozanide lesions in the human brain (Black et al., 2010; Figure 1). Astrocytes are not the sole nonexcitable cell type that displays a switch in sodium channel expression after pathological insult. The differentiation of human fibroblasts into myofibroblasts under pathological conditions is accompanied by de novo Nav1.5 expression (Chatelier et al., 2012) similar to that exhibited by reactive astrocytes. Müller cells, the primary macroglial cells in the retina, where they provide functional and metabolic support to neighboring neurons (Bringmann and Wiedemann, 2012), also exhibit increased sodium channel expression in response to injury (e.g., glaucoma, melanoma, retinal detachment) in that they express 4-fold larger sodium currents than do Müller cells from normal retinas (12.2 versus 3.0 pA/pF, respectively; Francke et al., 1996).