Release of intracellular calcium stores leads to retraction of membrane sheets and cell death in mature mouse oligodendrocytes.
The ability of mature oligodendrocytes (OLs) to recover from insult is important in repair of damage following demyelination. Since regulation of Ca2+ levels within cells plays a critical role in function and survival, this study investigates the effects of changes in cytoplasmic Ca2+ on the viability of cultured mouse OLs and their ability to maintain membrane sheets. Mature OLs in culture respond rapidly to the calcium ionophore A23187 and promptly return to resting Ca2+ levels when the ionophore is removed. Longer exposure to 0.1-1.0 microM A23187 leads to microtubule disruption, membrane sheet retraction and eventual cell death; nuclear lysis occurs in many of the OLs, as reported by Scolding, et al. (1) for rat OLs. In our cultures, mature OLs were more susceptible to nuclear lysis than were immature OLs or astroglia. Release of intracellular Ca2+ stores with thapsigargin at 5-10 microM also leads to retraction of membrane sheets. Following 6 hours of continuous exposure to thapsigargin, the effects on membrane sheets are reversed over the next 12 hours. After 18 hours of continuous exposure to thapsigargin, only occasional nuclear lysis is observed, but a number of the mature OLs show signs of DNA fragmentation, indicating that apoptotic death is occurring. Our results suggest that mature OLs cannot survive a prolonged influx of extracellular calcium as readily as immature OLs and astroglia, but have mechanism to withstand similar increases in cytoplasmic Ca2+ following sustained release of intracellular stores.
Benjamins
J A
JA
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Nedelkoska
L
L
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000166:cytology; D000001:Calcimycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D051379:Mice; D008807:Mice, Inbred BALB C; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D000001:Calcimycin; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D002118:Calcium