PURPOSE. Retinal ganglion cells are known to express ionotropic P2X 7 receptors for ATP. Stimulation of these receptors in other cells can elevate Ca 2ϩ and sometimes lead to cell death. This study asked whether P2X 7 receptor stimulation alters the Ca 2ϩ levels and viability of retinal ganglion cells. METHODS. P2X 7 agonists were applied to retinal ganglion cells from neonatal rats loaded with fura-2 to examine their effect on intracellular Ca 2ϩ levels. The effect of P2X 7 receptor

more »

... on cell viability was examined in rat retinal ganglion cells back-labeled with aminostilbamidine. RESULTS. The P2X 7 agonist benzoylbenzoyl adenosine triphosphate (BzATP) led to a large, sustained increase in Ca 2ϩ . BzATP was Ͼ100-fold more effective than ATP at raising intracellular Ca 2ϩ , when both agonists were applied at 10 M. The response to BzATP was enhanced threefold by removal of extracellular Mg 2ϩ , was dependent on extracellular Ca 2ϩ , and was prevented by brilliant blue G (BBG). BzATP led to a concentration-dependent reduction in the number of cells with a median lethal dose (LD 50 ) of 35 M. Cell death was prevented by the P2X 7 antagonists BBG and oxidized ATP, but not by 30 M suramin, consistent with the actions of the P2X 7 receptor. BzATP activated caspases in ganglion cells, but did not lead to membrane blebbing or increased permeability to Yo-Pro-1. The L-type Ca 2ϩ channel blocker nifedipine attenuated cell death, suggesting excessive Ca 2ϩ influx contributes to the lethal effects of BzATP. CONCLUSION. Short-term stimulation of the P2X 7 receptor can raise Ca 2ϩ in rat retinal ganglion cells, whereas sustained stimulation of the receptor can kill them. (Invest Ophthalmol Vis Sci. 2005;46:2183-2191