Extracellular calcium is a mediator of astroglial injury during combined glucose-oxygen deprivation.
We tested the hypothesis that extracellular calcium is a mediator of astroglial injury during combined glucose-oxygen deprivation. Both differentiated and undifferentiated astroglial cultures were exposed to combined glucose-oxygen deprivation in the presence and absence of extracellular calcium. Lactate dehydrogenase efflux was used as an index of cellular injury. Both types of cultures exhibited significantly less cellular injury when exposed to combined glucose-oxygen deprivation in the absence of extracellular calcium (e.g. lactate dehydrogenase efflux in undifferentiated cultures after 12 h of exposure: presence of calcium, 65.2 +/- 2.5% vs. absence of calcium, 21.4 +/- 1.3%). To further elucidate the mechanism by which extracellular calcium produces injury, we studied the effect of nimodipine, an L-type calcium channel blocker, on astroglial injury resulting from combined glucose-oxygen deprivation. Nimodipine decreased cellular injury in both types of cultures (e.g. lactate dehydrogenase efflux in undifferentiated cultures after 12 h of exposure: untreated, 65.4 +/- 2.2% vs. 10 nM nimodipine, 44.6 +/- 4.2%). Extracellular calcium appears to be a mediator of astroglial injury during combined glucose-oxygen deprivation. These results suggest that influx of extracellular calcium via L-type voltage-gated calcium channels may contribute to astroglial injury during cerebral ischemia.
Haun
S E
SE
Department of Pediatrics, Ohio State University, Columbus 43210.
Murphy
E J
EJ
Bates
C M
CM
Horrocks
L A
LA
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology*; D002454:Cell Differentiation; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007511:Ischemia; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004533:Egtazic Acid; D009553:Nimodipine; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D002118:Calcium