2. Academic Validation
  3. Potassium channel Kir 4.1 regulates oligodendrocyte differentiation via intracellular pH regulation

Potassium channel Kir 4.1 regulates oligodendrocyte differentiation via intracellular pH regulation

  • Glia. 2022 Nov;70(11):2093-2107. doi: 10.1002/glia.24240.
Na Wang 1,  Liang Zhou 1 2,  Chong-Yu Shao 1,  Xin-Tai Wang 1,  Nan Zhang 3,  Jiao Ma 3,  Hai-Lan Hu 4,  Yin Wang 3,  Mengsheng Qiu 5,  Ying Shen 1
Affiliations

Affiliations

  • 1 Department of Physiology and Department of Neurology of the First Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
  • 2 Key Laboratory of Brain Science, Guizhou Institution of Higher Education, Zunyi Medical University, Zunyi, China.
  • 3 Key Laboratory of Cranial Cerebral Diseases, Department of Neurobiology of Basic Medical College, Ningxia Medical University, Yinchuan, China.
  • 4 Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, China.
  • 5 Institute of Life Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
PMID: 35775976 DOI: 10.1002/glia.24240
Abstract

In humans, loss-of-function mutations of Kcnj10 in SeSAME/EAST syndrome, which encodes the inwardly rectifying K+ channel 4.1 (Kir 4.1), causes progressive neurological decline. Despite its rich expression in oligodendrocyte (OL) lineage cells and an emerging link with demyelinating disease, the function of Kir 4.1 in OLs is unclear. Here we show a novel role of Kir 4.1 in OL development. Kir 4.1 expression is markedly greater in OLs than in OL precursor cells (OPCs), and the down-regulation of Kir 4.1 impairs OL maturation by affecting OPC differentiation. Interestingly, Kir 4.1 regulates the intracellular pH of OPCs and OLs via the Na+ /H+ exchanger, which underlies impeded OPC differentiation by Kir 4.1 inhibition. Furthermore, Kir 4.1 regulates GSK3β and SOX10, two molecules critical to OPC development. Collectively, our work opens a new avenue to understanding the functions of Kir 4.1 and intracellular pH in OLs.

Keywords

Na+/H+ exchanger; inwardly-rectifying K+ channel; myelination; oligodendrocyte precursor cell; pH.

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