Effect of Ca2+ on in vitro astrocyte injury.
Current literature suggests that a massive influx of Ca2+ into the cells of the CNS induces cell damage associated with traumatic brain injury (TBI). Using an in vitro model for stretch-induced cell injury developed by our laboratory, we have investigated the role of extracellular Ca2+ in astrocyte injury. The degree of injury was assessed by measurement of propidium iodide uptake and release of lactate dehydrogenase. Based on results of in vivo models of TBI developed by others, our initial hypothesis was that decreasing extracellular Ca2+ would result in a reduction in astrocyte injury. Quite unexpectedly, our results indicate that decreasing extracellular Ca2+ to levels observed after in vivo TBI increased astrocyte injury. Elevating the extracellular Ca2+ content to twofold above physiological levels (2 mM) produced a reduction in cell injury. The reduction in injury afforded by Ca2+ could not be mimicked with Ba2+, Mn2+, Zn2+, or Mg2+, suggesting that a Ca(2+)-specific mechanism is involved. Using 45Ca2+, we demonstrate that injury induces a rapid influx of extracellular Ca2+ into the astrocyte, achieving an elevation in total cell-associated Ca2+ content two- to threefold above basal levels. Pharmacological elevation of intracellular Ca2+ levels with the Ca2+ ionophore A23187 or thapsigargin before injury dramatically reduced astrocyte injury. Our data suggest that, contrary to popular assumptions, an elevation of total cell-associated Ca2+ reduces astrocyte injury produced by a traumatic insult.
Rzigalinski
B A
BA
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Liang
S
S
McKinney
J S
JS
Willoughby
K A
KA
Ellis
E F
EF
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D051381:Rats; D013314:Stress, Mechanical; D013997:Time Factors
D002413:Cations, Divalent; D002118:Calcium