Quisqualate, high calcium concentration and zero-chloride prevent kainate-induced toxicity of cerebellar granule cells.
Kainic acid (KA; 100 microM), results in the death of all cultured rat cerebellar granule cells (18-22 days in vitro) within 30 min. Changes in the cells are evident within 2 min of applying the excitatory amino acid (EAA) and include an apparent cellular granulation with a loss of cell body birefringence at 10 X magnification. Quisqualic acid (QA; 25 microM) completely prevents this KA-induced neurotoxicity. In addition, cells are protected from toxicity by increasing calcium concentrations to 10 mM. Moreover, following a 30 min exposure and after washing the cells free of these compounds, cells placed in culture media remain alive 24 h later. Interestingly, neurons die when placed in a balanced salt solution which lacks calcium even when no KA is present. This death is also dependent on the presence of chloride and is prevented with the non-selective EAA antagonist, kynurenic acid, but is not prevented by QA. Collectively, these data suggest that the activation of the EAA receptor by KA in cerebellar granule cells is at least partially regulated by calcium and chloride and is suppressed by QA. Furthermore, placing granule cells in zero-calcium results in neuronal death which appears to be mediated by EAA mechanisms.
McCaslin
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Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Smith
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D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D002712:Chlorides / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology
D002132:Calcium Radioisotopes; D002712:Chlorides; D009467:Neuromuscular Depolarizing Agents; D010069:Oxadiazoles; D016318:Quisqualic Acid; D012964:Sodium; D006152:Cyclic GMP; D007608:Kainic Acid; D002118:Calcium