Glial Na⁺-dependent ion transporters in pathophysiological conditions

Sodium dynamics are essential for regulating functional processes in glial cells. Indeed, glial Na⁺ signaling influences and regulates important glial activities, and plays a role in neuron-glia interaction under physiological conditions or in response to injury of the central nervous system (CNS). Emerging studies indicate that Na⁺ pumps and Na⁺-dependent ion transporters in astrocytes, microglia, and oligodendrocytes regulate Na⁺ homeostasis and play a fundamental role in modulating glial activities in neurological diseases. In this review, we first briefly introduced the emerging roles of each glial cell type in the pathophysiology of cerebral ischemia, Alzheimer's disease, epilepsy, Parkinson's disease, Amyotrophic Lateral Sclerosis, and myelin diseases. Then, we discussed the current knowledge on the main roles played by the different glial Na⁺-dependent ion transporters, including Na⁺/K⁺ ATPase, Na⁺/Ca²⁺ exchangers, Na⁺/H⁺ exchangers, Na⁺-K⁺-Cl⁻ cotransporters, and Na⁺- HCO^- ₃ cotransporter in the pathophysiology of the diverse CNS diseases. We highlighted their contributions in cell survival, synaptic pathology, gliotransmission, pH homeostasis, and their role in glial activation, migration, gliosis, inflammation, and tissue repair processes. Therefore, this review summarizes the foundation work for targeting Na⁺-dependent ion transporters in glia as a novel strategy to control important glial activities associated with Na⁺ dynamics in different neurological disorders. GLIA 2016;64:1677–1697.