Scrapie prions alter receptor-mediated calcium responses in cultured cells
Kristensson, K.; Feuerstein, B.; Taraboulos, A.; Hyun, W.C.; Prusiner, S.B.; DeArmond, S.J.
Neurology 43(11): 2335-2341
1993
ISSN/ISBN: 0028-3878 PMID: 8232952 Document Number: 408600
The molecular basis of neurologic dysfunction in prion diseases is unknown. Spongiform degeneration of neurons is the most characteristic neuropathologic change which raises the possibility of abnormal ion channel function. Here we examined the regulation of Ca-2+ fluxes in two cell lines chronically infected with scrapie prions, designated ScN-2a (scrapie-infected mouse neuroblastoma) and ScHaB (scrapie-infected hamster brain) cells. In uninfected HaB cells, bradykinin caused increases in intracellular Ca-2+ concentration ((Ca-2+)-i) by release of Ca-2+ from internal stores and influx of extracellular Ca-2+ whereas, in N-2a cells, bradykinin increased (Ca-2+)-i exclusively from internal stores. Prion infection of both cell lines markedly reduced or eliminated bradykinin-activated increases in (Ca-2+)-i, whether driven by internal or extracellular sources. Stressing the cells with high extracellular (Ca-2+), 8 to 20 mM, led to cytopathologic changes in ScHaB but not in ScN-2a cells. Cytopathology was not preceded by an increase in (Ca-2+)-i. These findings indicate that scrapie infection induces abnormalities in receptor-mediated Ca-2+ responses and raise the possibility that nerve cell dysfunction and degeneration in prion diseases is related to ion channel aberrations.