CA2+ IONOPHORE-INDUCED APOPTOSIS ON CULTURED EMBRYONIC RAT CORTICAL-NEURONS

The neurotoxicity of ionomycin, a Ca2+ ionophore, was investigated in cultured cortical neurons from embryonic rats. While about 90% of neurons survived 2 h after exposure to ionomycin, the surviving neurons had decreased by about 30 to 40% at 16 h. Both RNA and protein synthesis inhibitors blocked this neurotoxicity. Furthermore, c-Fos immunoreactive neurons increased not only in number but also in the intensity of immunoreactivity. These results suggest that ionomycin-induced neuronal cell death is an active process which requires de novo transcription and translation. In addition, the ultrastructural changes, such as shrinkage of cell body, compaction of nucleus, condensation of chromatin, and membrane blebbing, were observed by electron microscopy. These morphological changes are indexes of apoptosis. Furthermore, DNA fragmentation, a biochemical marker of apoptosis, was also observed. All the results suggest that ionomycin-induced neuronal cell death is apoptotic.