Scrapie-infected GT1-1 cells show impaired function of voltage-gated N-type calcium channels (Ca(v) 2.2) which is ameliorated by quinacrine treatment.
Prions are transmissible pathogens that cause neurodegenerative diseases, although the mechanisms behind the nervous system dysfunctions are unclear. To study the effects of a prion infection on voltage-gated calcium channels, scrapie-infected gonadotropin-releasing hormone neuronal cells (ScGT1-1) in culture were depolarized by KCl and calcium responses recorded. Lower calcium responses were observed in infected compared to uninfected cells. This effect was still observed when L-type calcium channels were blocked by nimodipine. After inhibition of N-type calcium channels with omega-conotoxin GVIA, there was no difference in calcium responses. The calcium responses after nimodipine treatment became progressively lower during infection, but there was no major loss of the cellular prion protein (PrP(C)) or marked increase in accumulation of the abnormal prion protein (PrP(Sc)) in the cultures. These results indicate that scrapie infection causes a dysfunction of voltage-gated N-type calcium channels, which is exacerbated slowly over time. Quinacrine treatment cleared PrP(Sc) and restored calcium responses in the ScGT1-1 cultures.
Sandberg
Malin K
MK
Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Wallén
Peter
P
Wikström
Martin A
MA
Kristensson
Krister
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D018620:PrPSc Proteins / Q000187:drug effects / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology*; D012608:Scrapie / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004791:Enzyme Inhibitors; D018620:PrPSc Proteins; D011189:Potassium Chloride; D011796:Quinacrine; D002118:Calcium