Inward rectifying K_ir4.1 channels regulate oligodendrocyte precursor cell differentiation and CNS myelination in vivo

The functions of K_ir4.1 in oligodendrocyte development have been in controversial. We recently reported that inhibiting K_ir4.1 impeded oligodendrocyte precursor cell (OPC) differentiation and oligodendrocyte (OL) maturation, due to K_ir4.1 altering intracellular pH of OPCs through Na⁺/H⁺ exchangers. However, our conclusion was limited by in vitro observation, thereby it becomes necessary to seek in vivo evidence to determine the roles of K_ir4.1 on OPC development and CNS myelination. Here, we used Olig1-Cre to knockout K_ir4.1 in OPCs from the early developmental stage. We found that the cell-specific deletion of K_ir4.1 significantly impeded OPC differentiation and reduced the number of mature OLs in the cerebral cortex and the corpus callosum. Hence, our in vivo evidence supports that K_ir4.1 can regulate OPC differentiation and is essential to CNS myelination.