Potassium channel Kir 4.1 regulates oligodendrocyte differentiation via intracellular pH regulation
Na Wang1, Liang Zhou1,2, Chong-Yu Shao1
1Department 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.
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.
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