NR ALPB
AU Taylor,S.C.; Green,K.N.; Smith,I.F.; Peers,C.
TI Prion protein fragment 106-126 potentiates catecholamine secretion from PC-12 cells
QU American Journal of Physiology. Cell Physiology 2001 Dec; 281(6): C1850-7
PT journal article
AB The toxic actions of scrapie prion protein (PrPsc) are poorly understood. We investigated the ability of the toxic PrPsc 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 PrPsc.
MH Animal; Calcium Channel Blockers/pharmacology; Calcium Signaling/*physiology; Catecholamines/*secretion; Cations/metabolism; Exocytosis/physiology; PC12 Cells; Patch-Clamp Techniques; Peptide Fragments/*pharmacology; Potassium/metabolism; Prions/*pharmacology; Rats; Support, Non-U.S. Gov't
AD Institute for Cardiovascular Research, University of Leeds, Leeds LS2 9JT, United Kingdom.
SP englisch
PO USA