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

Feier Song,Yanfei Han,Jiayu Cao,Jieqing Wan,Xiaoping Tong,Zizhen Kang,Carlos Cepeda,Tianle Xu,Xiaoqi Hong,Guofen Ma,Shumin Duan

doi:10.1038/s42003-018-0083-x

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.

Highlights

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
A pioneer developmental study indicated that Kir4.1 could be immunoactivated in NG2+ glial cells in rat optic nerve[7], NG2glia, which are known as oligodendrocyte precursor cells (OPCs), until recently were found to express high levels of Kcnj[10] gene in juvenile mouse brain, as evidenced by RNA-Seq transcriptome analysis[8,9]
We investigate the role of Kir4.1 channels in NG2-glia during brain development, potassium signaling, and in ischemiarelated myelin loss

Summary

Introduction

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. Astrocytes in ipsilateral hippocampus of tMCAO mice did not show apparent reactive cell morphology nor any difference of Ba2+-sensitive Kir4.1 currents compared with that in the noninjured side[4,24] (Kir4.1 currents in astrocytes: contralateral, −558.5 ± 66.0 and 1135.8 ± 137.8 pA, n = 19 vs ipsilateral, −602.4 ± 82.8 and 1171.6 ± 224.5 pA, n = 14 at holding voltages of −140 and + 50 mV, respectively, P = 0.6745 at −140 mV and P = 0.8874 at +50 mV, two-tailed unpaired t-test, Fig. 3c, d).

Results

Conclusion