Details

Autor(en) / Beteiligte

• Korte, Stefan
• Vassallo, Neville
• Kramer, Michael L.
• Kretzschmar, Hans A.
• Herms, Jochen

Titel

Modulation of L‐type voltage‐gated calcium channels by recombinant prion protein

Ist Teil von

• Journal of neurochemistry, 2003-11, Vol.87 (4), p.1037-1042

Ort / Verlag

Oxford, UK: Blackwell Science Ltd

Erscheinungsjahr

2003

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• The prion protein (PrPC) has a primary role in the pathogenesis of transmissible spongiform encephalopathies. Here we analysed in detail the effect of recombinant PrPC and N‐ and C‐terminal fragments of PrPC on the whole‐cell current amplitude through voltage‐gated calcium channels (VGCCs) of cultured wild‐type cerebellar granule cells. With the application of full‐length recombinant PrPC (50–500 nm), a highly significant reduction of the whole‐cell current amplitude was observed in a dose‐dependent manner. Amplitude reduction was abolished when cells were pre‐incubated with nifedipine, a specific blocker of voltage‐gated L‐type calcium channels. N‐terminal PrP fragments also led to a dose‐dependent reduction of the maximal current amplitude, whereas a C‐terminal fragment did not affect the current amplitude. These data demonstrate that nanomolar concentrations of PrPC modulate L‐type VGCCs in mouse cerebellar granule cells, an effect that is dependent upon the copper‐binding amino‐terminal domain of PrPC.