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 ([Ca-i(2+)). Treatment of synaptosomes with bacterially derived recombinant human PrP in the range 20-100 mu g 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 [Ca-i(2+), 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.