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 and 60 minutes recovery. Treatment groups were exposed to ED following administration of the GABAA antagonist penicillin G (pc G) or substitution of extracellular chloride. The release of glutamate and GABA was measured by HPLC. The efflux of 36Cl from preloaded slices was measured during ED with and without blocking the GABAA receptor. The population spike disappeared during ED, and there was a marked release of GABA and glutamate. During recovery the population spike recovered partially. Both application of pc G and substitution of extracellular chloride during ED improved population spike recovery. Uptake of radiolabeled chloride was significantly reduced by pc G. Glutamate release, but not GABA, was significantly reduced by chloride substitution. These results indicate a possible role of chloride mediated injury during ED, and suggest that chloride entry may partly occur through ligand-operated channels. Furthermore there may be an early chloride dependent release of glutamate during cerebral ischemia, whereas later release seems to be chloride independent.
Grøndahl
T O
TO
Department of Neurosurgery, Rikshospitalet, National Hospital, Oslo, Norway.
Berg-Johnsen
J
J
Langmoen
I A
IA
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002712:Chlorides / Q000378:metabolism* / Q000493:pharmacokinetics / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D018757:GABA Modulators / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D010400:Penicillin G / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D002712:Chlorides; D018757:GABA Modulators; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D010400:Penicillin G