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Updated: Aug 30, 2026

Protein Misfolding Cyclic Amplification of Prions
Published on: November 7, 2012
Modulation of L-type voltage-gated calcium channels by recombinant prion protein
Stefan Korte1, Neville Vassallo, Michael L Kramer
1Department of Neuropathology, Ludwig-Maximilians-University München, München, Germany.
Abstract:
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.
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