title: Prion protein fragment 106-126 potentiates catecholamine secretion from PC-12 cells.
abstract: The toxic actions of scrapie prion protein (PrP(sc)) are poorly understood. We investigated the ability of the toxic PrP(sc) fragment 106-126 to interfere with evoked catecholamine secretion from PC-12 cells. Prion protein fragment 106-126 (PrP106-126) caused a time- and concentration-dependent augmentation of exocytosis due to the emergence of a Ca(2+) influx pathway resistant to Cd(2+) but sensitive to other inorganic cations. In control cells, secretion was dependent on Ca(2+) influx through L- and N-type Ca(2+) channels, but after exposure to PrP106-126, secretion was unaffected by N-type channel blockade. Instead, selective L-type channel blockade was as effective as Cd(2+) in suppressing secretion. Patch-clamp recordings revealed no change in total Ca(2+) current density in PrP106-126-treated cells or in the contribution to total current of L-type channels, but a small Cd(2+)-resistant current was found only in PrP106-126-treated cells. Thus PrP106-126 augments secretion by inducing a Cd(2+)-resistant Ca(2+) influx pathway and alters coupling of native Ca(2+) channels to exocytosis. These effects are likely contributory factors in the toxic cellular actions of PrP(sc).
authors.affiliation: Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Taylor
authors.forename: K N
authors.initials: KN
authors.lastname: Green
authors.forename: I F
authors.initials: IF
authors.lastname: Smith
authors.forename: C
authors.initials: C
authors.lastname: Peers
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000502:physiology*; D002395:Catecholamines / Q000378:metabolism*; D002412:Cations / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011328:Prions / Q000494:pharmacology*; D051381:Rats
chemical_list: D002121:Calcium Channel Blockers; D002395:Catecholamines; D002412:Cations; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); D011188:Potassium