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Modulation of L ‐type voltage‐gated calcium channels by recombinant prion protein
Author(s) -
Korte Stefan,
Vassallo Neville,
Kramer Michael L.,
Kretzschmar Hans A.,
Herms Jochen
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02080.x
Subject(s) - recombinant dna , modulation (music) , chemistry , calcium , voltage dependent calcium channel , biophysics , microbiology and biotechnology , biochemistry , biology , physics , gene , organic chemistry , acoustics
The prion protein (PrP C ) has a primary role in the pathogenesis of transmissible spongiform encephalopathies. Here we analysed in detail the effect of recombinant PrP C and N‐ and C‐terminal fragments of PrP C 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 PrP C (50–500 n m ), 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 PrP C modulate L ‐type VGCCs in mouse cerebellar granule cells, an effect that is dependent upon the copper‐binding amino‐terminal domain of PrP C .