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

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

doi:10.1038/s42003-018-0083-x

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

Commun Biol. 2018 Jun 28:1:80. doi: 10.1038/s42003-018-0083-x. eCollection 2018.

Authors

Feier Song¹, Xiaoqi Hong¹, Jiayu Cao², Guofen Ma¹, Yanfei Han¹, Carlos Cepeda³, Zizhen Kang⁴, Tianle Xu¹, Shumin Duan⁵, Jieqing Wan⁶, Xiaoping Tong⁷

Affiliations

¹ Discipline of Neuroscience and Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
² Department of Neurosurgery, Shanghai Ren Ji Hospital, Shanghai, 200127, China.
³ Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles School of Medicine, Los Angeles, 90024, CA, USA.
⁴ Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
⁵ Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou, 310058, China.
⁶ Department of Neurosurgery, Shanghai Ren Ji Hospital, Shanghai, 200127, China. jieqingwan@126.com.
⁷ Discipline of Neuroscience and Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. xtong@shsmu.edu.cn.

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.