Neurotoxicity of calcium ionophore A23187 in immature rat cerebellar slices.
The causal role of Ca2+ in neuronal necrosis is controversial and it has been suggested that neuronal Ca2+ uptake is only a secondary effect to cell death. Here, I address this question directly by studying the morphological effects of calcium ionophore A23187 on immature cerebellar slices. Parasagittal slices were prepared and incubated for 30, 90 or 120 min in physiological saline with or without A23187. In some cases Ca2+ was omitted from the incubation medium. Slices were processed for light microscopy. A23187 produced nuclear changes indicative of cell death that encompassed cells of the external granule cell layer at short incubation times (30 min) and more deeply situated cells at longer times (120 min). This indicates that A23187 diffusion is limited in the slice. The histological changes produced by 30 min exposure to the ionophore could not be reversed by incubation for 90 min in normal medium. Necrosis was never observed when slices were exposed to A23187 in Ca2+-free medium. The results demonstrate that influx of excessive amounts of Ca2+ kills cells of the central nervous system.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000001:Calcimycin; D002118:Calcium