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.
Whatley
S A
SA
Department of Neuroscience, Institute of Psychiatry, London, UK.
Powell
J F
JF
Politopoulou
G
G
Campbell
I C
IC
Brammer
M J
MJ
Percy
N S
NS
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D016133:Polymerase Chain Reaction; D018621:PrPC Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018621:PrPC Proteins; D011994:Recombinant Proteins; D005682:Gadolinium; C038958:gadolinium chloride; D002118:Calcium