Scrapie prions alter receptor-mediated calcium responses in cultured cells

K. Kristensson, Burt G.F. Feuerstein, A. Taraboulos, W. C. Hyun, S. B. Prusiner, S. J. DeArmond

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2335-2341
Number of pages7
JournalNeurology
Volume43
Issue number11
StatePublished - Nov 1993
Externally publishedYes

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Calcium-Sensing Receptors
Scrapie
Prions
Cultured Cells
Bradykinin
Nerve Degeneration
Prion Diseases
Ion Channels
Cricetinae
Cell Line
Brain
Neurologic Manifestations
Infection
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kristensson, K., Feuerstein, B. G. F., Taraboulos, A., Hyun, W. C., Prusiner, S. B., & DeArmond, S. J. (1993). Scrapie prions alter receptor-mediated calcium responses in cultured cells. Neurology, 43(11), 2335-2341.

Scrapie prions alter receptor-mediated calcium responses in cultured cells. / Kristensson, K.; Feuerstein, Burt G.F.; Taraboulos, A.; Hyun, W. C.; Prusiner, S. B.; DeArmond, S. J.

In: Neurology, Vol. 43, No. 11, 11.1993, p. 2335-2341.

Research output: Contribution to journalArticle

Kristensson, K, Feuerstein, BGF, Taraboulos, A, Hyun, WC, Prusiner, SB & DeArmond, SJ 1993, 'Scrapie prions alter receptor-mediated calcium responses in cultured cells', Neurology, vol. 43, no. 11, pp. 2335-2341.
Kristensson K, Feuerstein BGF, Taraboulos A, Hyun WC, Prusiner SB, DeArmond SJ. Scrapie prions alter receptor-mediated calcium responses in cultured cells. Neurology. 1993 Nov;43(11):2335-2341.
Kristensson, K. ; Feuerstein, Burt G.F. ; Taraboulos, A. ; Hyun, W. C. ; Prusiner, S. B. ; DeArmond, S. J. / Scrapie prions alter receptor-mediated calcium responses in cultured cells. In: Neurology. 1993 ; Vol. 43, No. 11. pp. 2335-2341.
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