Ca2+ entry via AMPA/KA receptors and excitotoxicity in cultured cerebellar Purkinje cells

摘要: Initial studies of glutamate receptors activated by kainate (KA) found them to be Ca2+ impermeable. Activation these was thought produce influx into neurons only indirectly Na(+)-dependent depolarization. However, entry via AMPA/KA has now been demonstrated in several neuronal types, including cerebellar Purkinje cells. We have investigated whether such is sufficient induce excitotoxicity cultures enriched for Agonists at non-NMDA induced the majority cells, as measured whole-cell voltage clamp and fura-2 [Ca2+]i microfluorimetry. To assess excitotoxicity, were exposed agonists 20 min cell survival evaluated a fluorescence assay 24 hr later. KA (100 microM) reduced relative controls 43 +/- 3% when applied Na(+)-containing solution 45 Na(+)-free solution. This toxicity blocked completely CNQX but slightly 100 microM Cd2+ 50 D-(-)-2-amino-5-phosphonovaleric acid. Both non-Purkinje types present similarly vulnerable toxic exposure, population marked KA-induced Co2+ uptake selectively diminished excitotoxicity. Na(+)-independent could also domoate, AMPA, or glutamate. Compared KA, NMDA relatively ineffective inducing death. Most removal extracellular during exposure 5 period thereafter. Furthermore, antagonists Ca(2+)-activated enzymes nitric oxide synthase calpain significantly These results show that receptor activation can cause mechanisms not involving Na+ influx, rather depending on direct permeation Ca(2+)- dependent enzymatic processes.