Heterogeneity in oligodendrocyte precursor cell proliferation is dynamic and driven by passive bioelectrical properties

Oligodendrocyte precursor cells (OPCs) generate myelinating oligodendrocytes and are the main proliferative cells in the adult central nervous system. OPCs are a heterogeneous population, with proliferation and differentiation capacity varying with brain region and age. We demonstrate that during early postnatal maturation, cortical, but not callosal, OPCs begin to show altered passive bioelectrical properties, particularly increased inward potassium (K⁺) conductance, which correlates with G1 cell cycle stage and affects their proliferation potential. Neuronal activity-evoked transient K⁺ currents in OPCs with high inward K⁺ conductance potentially release OPCs from cell cycle arrest. Eventually, OPCs in all regions acquire high inward K⁺ conductance, the magnitude of which may underlie differences in OPC proliferation between regions, with cells being pushed into a dormant state as they acquire high inward K⁺ conductance and released from dormancy by synchronous neuronal activity. Age-related accumulation of OPCs with high inward K⁺ conductance might contribute to differentiation failure.