title: The prion peptide forms ion channels in planar lipid bilayers.
abstract: One of the hypotheses concerning the pathogenic properties of the prion protein considers its influence on cellular ion homeostasis. Using the lipid bilayer technique, the influence of prion-derived peptides on the lipid bilayer conductance was characterized. To evaluate the physiological significance and possible pathological functions of the peptides, their effect on the membrane potential and respiration rate of hippocampal mitochondria was also studied. We used a peptide bearing the human prion protein sequence YSNQNNF (PrP [169-175]), and peptide SSQNNF (PrP [170-175]) bearing a naturally-occurring mutation in position 171 [N(r)S] linked to schizoaffective diseases in humans (Samaia, H.B., Mari, J.J., Vallada, H.P., Moura R.P., Simpson A.J.G., Brentani R.R. A prion-linked psychiatric disorder. Nature 390 (1997) 241). In this report, we show that PrP [170-175] N171S increases the conductance of planar lipid bilayers. Based on the conductance of single channel currents recorded in 500/500 mM KCl (cis/trans), we found a single channel conductance of 8 to 26 pS. The native prion peptide PrP [169-175] does not form ion channels in the lipid bilayer. Neither of the peptides significantly changed the membrane potential or respiration rate of isolated rat hippocampal mitochondria. We propose a possible mechanism for channel formation by aggregation of the prion-derived peptide.
authors.affiliation: Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, 02-093 Warszawa, Poland.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berest
authors.forename: Marcin
authors.initials: M
authors.lastname: Rutkowski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Rolka
authors.forename: Anna
authors.initials: A
authors.lastname: Łegowska
authors.forename: Grazyna
authors.initials: G
authors.lastname: Debska
authors.forename: Dariusz
authors.initials: D
authors.lastname: Stepkowski
authors.forename: Adam
authors.initials: A
authors.lastname: Szewczyk
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006624:Hippocampus / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D010455:Peptides; D011328:Prions