Regulation of intracellular free calcium levels by the cellular prion protein.

A rat brain synaptosomal model was used to investigate the possible role of the cellular prion protein (PrP) in the regulation of intracellular free calcium levels ([Ca2+i). Treatment of synaptosomes with bacterially derived recombinant human PrP in the range 20-100 micrograms ml-1 resulted in dose-dependent elevations of [Ca2+]i. These increases were dependent on extracellular calcium and were inhibited by gadolinium chloride, a potent blocker of voltage-sensitive calcium channels. Conversely, when calcium channels were activated by synaptosomal depolarization, treatment with monoclonal antibody to PrP in the range 200-320 ng IgG ml-1 resulted in a dose-dependent reduction of [Ca2+i, which was blocked by competition with PrP preparations. These results indicate that PrP is associated with regulation of intracellular free calcium levels through an interaction with voltage-sensitive calcium channels.