Fig. 3. Proposed physiological roles of NCX activities in cells of the OLG lineage.

A: For OPCs located in the postnatal subventricular zone (SVZ), activation of GABA_A receptors has been reported to induce a chemotactic migration response that is mediated by calcium influx via reverse mode NCX1 activity triggered by sodium influx through non-inactivating sodium channels (Na_v) after GABA-induced membrane depolarization [99]. B: For differentiating and myelinating OLGs, a differentiation promoting role emerges for NCX3 [101, 102]. Thus far, two neuronal activity-induced pathways have been proposed. First, OLG membrane depolarization-induced reverse mode NCX activity has been implicated in promoting the syntheses of the myelin protein myelin basic protein (MBP) and the processes of active myelination [106, 107]. Second, activation of sodium-dependent glutamate transporters (EAAT), presumably through glutamate release from electrically active axons, was found to promote the morphological maturation of differentiating OLGs by a molecular mechanism involving reverse mode NCX activity and an increase in intracellular calcium concentration (Fig. 2) [109, 110].