Previous investigations have shown that phorbol esters stimulate process extension in oligodendrocytes (OL), likely by the activation of protein kinase C (PKC). In this report, we demonstrate that treatment of OL with 4beta-phorbol-12, 13-dibutyrate (PDB; 0.1-1 microM) resulted in an increase in intracellular Ca2+ concentration ([Ca2+]i) from 94+/-2 nM (mean+/-S.E.M.) to 244+/-10 nM. This increase was produced by Ca2+ influx through a La3+-insensitive pathway. Changes in [Ca2+]i were also produced by modifying the extracellular Ca2+ concentration ([Ca2+]o) where [Ca2+]i was increased by elevations in [Ca2+]o. In parallel experiments we found that increased [Ca2+]o alone, without concurrent phorbol ester application, resulted in increased OL process extension as determined by the percent of OL with long processes (greater than 3 times the cell body diameter). These results demonstrate that increasing [Ca2+]o stimulates OL process outgrowth. Furthermore, both elevations in [Ca2+]o and PDB exposure increase [Ca2+]i, suggesting that some of the effects of phorbol esters on OL process extension are likely mediated by changes in [Ca2+]i.
Copyright 1999 Elsevier Science B.V.