NR APIW
AU Korte,S.; Vassallo,N.; Kramer,M.L.; Kretzschmar,H.A.; Herms,J.W.
TI Modulation of L-type voltage-gated calcium channels by recombinant prion protein
QU Journal of Neurochemistry 2003 Nov; 87(4): 1037-42
PT journal article
AB 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.
MH Animals; Calcium/metabolism; Calcium Channels, L-Type/drug effects/*metabolism; Cells, Cultured; Cerebellum/cytology; Copper/pharmacology; Dose-Response Relationship, Drug; Ion Transport/drug effects/physiology; Kinetics; Mice; Mice, Inbred Strains; Neurons/cytology/drug effects/*metabolism; Patch-Clamp Techniques; Peptide Fragments/genetics/metabolism/pharmacology; PrPc Proteins/genetics/*metabolism/pharmacology; Protein Structure, Tertiary/physiology; Support, Non-U.S. Gov't
AD Department of Neuropathology, Ludwig-Maximilians-University München, München, Germany.
SP englisch
PO England