Changes in intracellular Ca2+ play a key role in regulating gene expression and developmental changes in oligodendroglial precursor cells (OPCs). However, the mechanisms by which Ca2+ influx in OPCs is controlled remains incompletely understood. Although there are several mechanisms that modulate Ca2+ influx, in many systems the large-conductance, voltage- and Ca2+-activated K+ channel (BK channel) plays an important role in regulating both membrane excitability and intracellular Ca2+ levels. To date, the role of the BK channel in the regulation of intracellular Ca2+ in oligodendroglial lineage cells is unknown. Here we investigated whether cells of the oligodendroglial lineage express BK channels and what potential role they play in regulation of Ca2+ influx in these cells. In oligodendrocytes derived from differentiated adult neural precursor cells (NPCs, obtained from C57bl6 mice) we observed outward currents that were sensitive to the BK channel blocker iberiotoxin (IbTx). Further confirmation of the expression of the BK channel was obtained utilizing other blockers of the BK channel and by confocal immunofluoresence labelling of the BK channel on oligodendroglia. Using Fura-2AM to monitor intracellular Ca2+, it was observed that inhibition of the BK channel during glutamate-induced depolarization led to an additive increase in intracellular Ca2+ levels. Electrophysiological difference currents demonstrated that the expression levels of the BK channel decrease with developmental age. This latter finding was further corroborated via RT-PCR and Western blot analysis. We conclude that the BK channel is involved in regulating Ca2+ influx in OPCs, and may potentially play a role during differentiation of oligodendroglial lineage cells.