During myelinogenesis, we found an exceedingly strong, transient expression of the alpha(1E) gene for the R-type voltage-gated calcium channel in CNS white matter. This immunoreactivity appeared in glial cells along specific pathways of the brainstem, cerebellum, and telencephalon. The reactivity followed a wave that progressed from the brainstem at P5, to the cerebellar peduncles by P8, the arbor vitae by P14, and the granular layer by P17. The reactivity-peaked about 3-4 days later and decreased gradually to become negligible in all areas before adulthood. Ultrastructural analysis confirmed that alpha(1E) immunoreactivity was located in oligodendroglial somata, their projections, paranodal wraps and loose myelin sheaths. There was a distinct association of the channel protein reactivity on oligodendroglial membranes in contact with the axon. We propose that glial projections, contacting axons, sense axonal firing through small K(+) currents and open the high voltage R-type calcium channels to signal myelination.