Potassium channel K <sub>ir</sub> 4.1 regulates oligodendrocyte differentiation via intracellular <scp>pH</scp> regulation
Na Wang, Liang Zhou, Chongyu Shao, Xin‐Tai Wang, Nan Zhang, Jiao Ma, Hailan Hu, Yin Wang, Mengsheng Qiu, Ying Shen
Abstract
Abstract In humans, loss‐of‐function mutations of Kcnj10 in SeSAME/EAST syndrome, which encodes the inwardly rectifying K + channel 4.1 (K ir 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 K ir 4.1 in OLs is unclear. Here we show a novel role of K ir 4.1 in OL development. K ir 4.1 expression is markedly greater in OLs than in OL precursor cells (OPCs), and the down‐regulation of K ir 4.1 impairs OL maturation by affecting OPC differentiation. Interestingly, K ir 4.1 regulates the intracellular pH of OPCs and OLs via the Na + /H + exchanger, which underlies impeded OPC differentiation by K ir 4.1 inhibition. Furthermore, K ir 4.1 regulates GSK3β and SOX10, two molecules critical to OPC development. Collectively, our work opens a new avenue to understanding the functions of K ir 4.1 and intracellular pH in OLs.