Abstract:

NG2 cells originate from various brain regions and migrate to their destinations during early development. These cells express voltage-gated Na⁺ channels but fail to produce typical action potentials. The physiological role of Na⁺ channels in these cells is unclear. We found that GABA induces membrane depolarization and Ca²⁺ elevation in NG2 cells, a process requiring activation of GABA_A receptors, Na⁺ channels, and Na⁺/Ca²⁺ exchangers (NCXs), but not Ca²⁺ channels. We have identified a persistent Na⁺ current in these cells that may underlie the GABA-induced pathway of prolonged Na⁺ elevation, which in turn triggers Ca²⁺ influx via NCXs. This unique Ca²⁺ signaling pathway is further shown to be involved in the migration of NG2 cells. Thus, GABAergic signaling mediated by sequential activation of GABA_A receptors, noninactivating Na⁺ channels, and NCXs may play an important role in the development and function of NG2 glial cells in the brain.