Raising intracellular calcium attenuates neuronal apoptosis triggered by staurosporine or oxygen-glucose deprivation in the presence of glutamate receptor blockade.

The relationship between intracellular Ca(2+) (Ca(2+)) regulation and programmed cell death is not well-defined; both increases and decreases in Ca(2+) have been observed in cells undergoing apoptosis. We determined Ca(2+) in cultured murine cortical neurons undergoing apoptosis after exposure to staurosporine or following oxygen-glucose deprivation in the presence of glutamate receptor antagonists. Neuronal Ca(2+) was decreased 1-4 h after exposure to staurosporine (30 nM). A Ca(2+) decrease was also observed 1 h after the end of the oxygen-glucose deprivation period when MK-801 and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were added to the bathing medium during the deprivation period. A similar decrease in Ca(2+) produced by reducing extracellular Ca(2+) or chelating intracellular Ca(2+) was sufficient to induce neuronal apoptosis. Raising Ca(2+) either by activating voltage-sensitive Ca(2+) channels with (-) Bay K8644 or by application of low concentrations of kainate attenuated both staurosporine and oxygen-glucose deprivation-induced apoptosis.