Cytotoxic effect of Ca++ released from intracellular stores during cerebral energy deprivation.
The increase in cytoplasmatic calcium concentration during cerebral ischemia has been proposed as a key event leading to neuronal death. In order to investigate a possible role of calcium-release from intracellular stores in ischemic neuronal injury, intracellular calcium pools were depleted prior to ischemia by the use of thapsigargin. Evoked activity (population spike) in rat hippocampal slices was monitored during a 30 min control period, 9 min of energy deprivation and 60 min of recovery. The population spike recovered to 27% (17-33) (median and 95% confidence interval) following energy deprivation in normal calcium, to 56% (50-58) in calcium-free incubation fluid and to 83% (75-88) in slices pretreated with 1 microM thapsigargin. Combining calcium removal and thapsigargin pretreatment did not improve recovery further. Both removal of extracellular calcium and emptying intracellular calcium stores prior to energy deprivation thus improved functional recovery following energy deprivation, however the latter was more effective. These results suggest that calcium release from intracellular stores may be of major importance in calcium-related neuronal injury during cerebral ischemia.
Grøndahl
T O
TO
Department of Neurosurgery, Rikshospitalet, National Hospital, University of Oslo, Norway.
Langmoen
I A
IA
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism / Q000633:toxicity*; D003603:Cytotoxins / Q000378:metabolism* / Q000633:toxicity; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
D003603:Cytotoxins; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D000255:Adenosine Triphosphate; D002118:Calcium