CHLORIDE INFLUX DURING CEREBRAL ENERGY DEPRIVATION

The purpose of the present study was to investigate the possible role of chloride influx and GABA release during cerebral energy deprivation (ED). The functional activity measured by evoked activity (population spike) in hippocampal slices was recorded during nine minutes of ED a nd 60 minutes recovery. Treatment groups were exposed to ED following administration of the GABA(A) antagonist penicillin G (pcG) or substit ution of extracellular chloride. The release of glutamate and GABA was measured by HPLC. The efflux of Cl-36 from preloaded slices was measu red during ED with and without blocking the GABA(A) receptor. The popu lation spike disappeared during ED, and there was a marked release of GABA and glutamate. During recovery the population spike recovered par tially. Both application of pcG and substitution of extracellular chlo ride during ED improved population spike recovery. Uptake of radiolabe led chloride was significantly reduced by pcG. Glutamate release, but not GABA, was significantly reduced by chloride substitution. These re sults indicate a possible role of chloride mediated injury during ED, and suggest that chloride entry may par?ly occur through ligand-operat ed channels. Furthermore there may be an early chloride dependent rele ase of glutamate during cerebral ischemia, whereas later release seems to be chloride independent.