SCRAPIE PRIONS ALTER RECEPTOR-MEDIATED CALCIUM RESPONSES IN CULTURED-CELLS

The molecular basis of neurologic dysfunction in prion diseases is unk nown. Spongiform degeneration of neurons is the most characteristic ne uropathologic change which raises the possibility of abnormal ion chan nel function. Here we examined the regulation of Ca2+ fluxes in two ce ll lines chronically infected with scrapie prions, designated ScN2a (s crapie-infected mouse neuroblatoma) and ScHaB (scrapie-infected hamste r brain) cells. In uninfected HaB cells, bradykinin caused increases i n intracellular Ca2, concentration ([Ca2+]i) by release of Ca2+ from i nternal stores and influx of extracellular Ca2+ whereas, in N2a cells, bradykinin increased [Ca2+]i exclusively from internal stores. Prion infection of both cell lines markedly reduced or eliminated bradykinin -activated increases in [Ca2+]i, whether driven by internal or extrace llular sources. Stressing the cells with high extracellular [Ca2+], 8 to 20 mM, led to cytopathologic changes in ScHaB but not in ScN2a cell s. Cytopathology was not preceded by an increase in [Ca2+]i. These fin dings indicate that scrapie infection induces abnormalities in recepto r-mediated Ca2+ responses and raise the possibility that nerve cell dy sfunction and degeneration in prion diseases is related to ion channel aberrations.