GABA accelerates excitotoxic cell death in cortical cultures: protection by blockers of GABA-gated chloride channels.
The effects of gamma-aminobutyric acid (GABA) and related agonists and antagonists on the excitatory cell death were examined in dispersed primary cultures of the rat cerebral cortex. The cytotoxic effects evoked by kainic acid, quisqualic acid and N-methyl-D-aspartic acid were evaluated by phase contrast microscopy and quantified by the measurement of lactic dehydrogenase release into the culture medium. GABA accelerated the cell death in a concentration-dependent fashion, but did not influence the amount of cells dying with 24 h after the treatment. This effect of GABA could be mimicked by GABAA rather than GABAB receptor agonists. Blockers acting at different sites of the GABAA receptor/chloride channel complex not only reduced the GABA-induced acceleration of cell death, but also showed a significant protection against the excitotoxic cell death in the absence of exogenous GABA. Blockers of chloride channels unrelated to GABA receptors produced similar protection. Our findings indicate that GABA-gated chloride channels may be effective in modulating excitotoxic vulnerability of cerebrocortical cells.
Erdö
S
S
Department of Anatomy, Georg-August University, Göttingen, F.R.G.
Michler
A
A
Wolff
J R
JR
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D015640:Ion Channel Gating; D007608:Kainic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D016202:N-Methylaspartate / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D009498:Neurotoxins; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D007608:Kainic Acid