Apoptotic cell death and impairment of L-type voltage-sensitive calcium channel activity in cerebellar granule cells treated with the prion protein fragment 106-126

Stefano Thellung, Tullio Florio, Valentina Villa, Alessandro Corsaro, Sara Arena, Carolina Amico, Mauro Robello, Mario Salmona, Gianluigi Forloni, Orso Bugiani, Fabrizio Tagliavini, Gennaro Schettini

Research output: Contribution to journalArticle

Abstract

Prion diseases are neurodegenerative pathologies characterized by the accumulation, in the brain, of altered forms of the prion protein (PrP), named PrP(Sc). A synthetic peptide homologous to residues 108-126 of PrP (PrP108-126) was reported to maintain the neurodegenerative characteristics of PrP(Sc). We investigated the intracellular mechanisms involved in PrP106-126-dependent degeneration of primary cultures of cerabellar granule neurons. Prolonged exposure of such neurons to PrP106-126 induced apoptotic cell death. The L-type voltage-sensitive calcium channel blocker nicardipine reproduced this effect, suggesting that blockade of Ca2+ entry through this class of calcium channels may be responsible for the granule cell degeneration. Microfluorometric analysis showed that PrP106-126 caused a reduction in cytosolic calcium levels, elicited by depolarizing K+ concentrations in these neurons. Electrophysiological studies demonstrated that PrP106-126 and nicardipine selectively reduce the L-type calcium channel currant. These data demonstrate that PrP106-126 alters the activity of L-type voltage-sensitive calcium channels in rat cerebellar granule cells and suggest that this phenomenon is related to the cell death induced by the pepfide. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)299-309
Number of pages11
JournalNeurobiology of Disease
Volume7
Issue number4
DOIs
Publication statusPublished - 2000

Keywords

  • Apoptosis
  • L-type voltage-sensitive calcium channels
  • Nicardipine
  • Prion protein

ASJC Scopus subject areas

  • Neurology

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