Kir4.1 channels in NG2-glia play a role in development, potassium signaling, and ischemia-related myelin loss

Abstract

The contribution of the inwardly rectifying K⁺ channel subtype Kir4.1 has been focused mainly on astrocytes, where they play important roles in the maintenance of resting membrane potential, extracellular K⁺ uptake, and facilitation of glutamate uptake in the central nervous system. Here, we report the role of Kir4.1 channels in NG2-glia during brain development, potassium signaling, and in an ischemic stroke disease model. Kir4.1 channels are widely expressed in NG2-glia during brain development. In the adult mouse hippocampus, Kir4.1 channels in NG2-glia constitute more than 80% of K⁺ channels inward currents. This large portion of Kir4.1 channel currents exhibits a deficit in NG2-glia as an initial response in a transient ischemic mouse model. Further evidence indicates that Kir4.1 deficits in NG2-glia potentially cause axonal myelin loss in ischemia through the association with oligodendrocyte-specific protein (OSP/Claudin-11), which unravels a potential therapeutic target in the treatment of ischemic stroke.

Feier Song and colleagues have examined Kir4.1 channels in the mouse brain, and found global expression of functional channels during development. They also show that depletion of Kir4.1 channels impacts demyelination in ischemic stroke