Regulation of intracellular free calcium levels by the cellular prion protein

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Abstract
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 μg 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.

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