Scrapie prions alter receptor-mediated calcium responses in cultured cells.
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 Ca2+ fluxes in two cell lines chronically infected with scrapie prions, designated ScN2a (scrapie-infected mouse neuroblatoma) and ScHaB (scrapie-infected hamster brain) cells. In uninfected HaB cells, bradykinin caused increases in intracellular Ca2+ concentration ([Ca2+]i) by release of Ca2+ from internal 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 extracellular sources. Stressing the cells with high extracellular [Ca2+], 8 to 20 mM, led to cytopathologic changes in ScHaB but not in ScN2a cells. Cytopathology was not preceded by an increase in [Ca2+]i. These findings indicate that scrapie infection induces abnormalities in receptor-mediated Ca2+ responses and raise the possibility that nerve cell dysfunction and degeneration in prion diseases is related to ion channel aberrations.
Kristensson
K
K
Department of Neurology, University of California, San Francisco 94143-0506.
Feuerstein
B
B
Taraboulos
A
A
Hyun
W C
WC
Prusiner
S B
SB
DeArmond
S J
SJ
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D008647:Mesocricetus; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000382:microbiology*; D011328:Prions / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D011328:Prions; D011956:Receptors, Cell Surface; D001920:Bradykinin; D002118:Calcium