Sodium–Calcium Exchangers of the SLC8 Family in Oligodendrocytes: Functional Properties in Health and Disease

Abstract

The solute carrier 8 (SLC8) family of sodium–calcium exchangers (NCXs) functions as an essential regulatory system that couples opposite fluxes of sodium and calcium ions across plasmalemmal membranes. NCXs, thereby, play key roles in maintaining an ion homeostasis that preserves cellular integrity. Hence, alterations in NCX expression and regulation have been found to lead to ionic imbalances that are often associated with intracellular calcium overload and cell death. On the other hand, intracellular calcium has been identified as a key driver for a multitude of downstream signaling events that are crucial for proper functioning of biological systems, thus highlighting the need for a tightly controlled balance. In the CNS, NCXs have been primarily characterized in the context of synaptic transmission and ischemic brain damage. However, a much broader picture is emerging. NCXs are expressed by virtually all cells of the CNS including oligodendrocytes (OLGs), the cells that generate the myelin sheath. With a growing appreciation of dynamic calcium signals in OLGs, NCXs are becoming increasingly recognized for their crucial roles in shaping OLG function under both physiological and pathophysiological conditions. In order to provide a current update, this review focuses on the importance of NCXs in cells of the OLG lineage. More specifically, it provides a brief introduction into plasmalemmal NCXs and their modes of activity, and it discusses the roles of OLG expressed NCXs in regulating CNS myelination and in contributing to CNS pathologies associated with detrimental effects on OLG lineage cells.