CYTOTOXIC EFFECT OF CA++ RELEASED FROM INTRACELLULAR STORES DURING CEREBRAL ENERGY DEPRIVATION

The increase in cytoplasmatic calcium concentration during cerebral is chemia has been proposed as a key event leading to neuronal death. In order to investigate a possible role of calcium-release from intracell ular stores in ischemic neuronal injury, intracellular calcium pools w ere depleted prior to ischemia by the use of thapsigargin. Evoked acti vity (population spike) in rat hippocampal slices was monitored during a 30 min control period 9 min of energy deprivation and 60 min of rec overy. The population spike recovered to 27% (17-33) (median and 95% c onfidence interval) following energy deprivation in normal calcium, to 56% (50-58) in calcium-free incubation fluid and to 83% (75-88) in sl ices pretreated with 1 mu M thapsigargin. Combining calcium removal an d thapsigargin pretreatment did not improve recovery further. Both rem oval of extracellular calcium and emptying intracellular calcium store s prior to energy deprivation thus improved functional recovery follow ing energy deprivation, however the latter was more effective. These r esults suggest that calcium release from intracellular stores may be o f major importance in calcium-related neuronal injury during cerebral ischemia.