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- Title
Plasma membrane ion permeability induced by mutant α-synuclein contributes to the degeneration of neural cells.
- Authors
Furukawa, Katsutoshi; Matsuzaki-Kobayashi, Michiko; Hasegawa, Takafumi; Kikuchi, Akio; Sugeno, Naoto; Itoyama, Yasuto; Yue Wang; Yao, Pamela J.; Bushlin, Ittai; Takeda, Atsushi
- Abstract
Mutations in α-synuclein cause some cases of familial Parkinson's disease (PD), but the mechanism by which α-synuclein promotes degeneration of dopamine-producing neurons is unknown. We report that human neural cells expressing mutant α-synuclein (A30P and A53T) have higher plasma membrane ion permeability. The higher ion permeability caused by mutant α-synuclein would be because of relatively large pores through which most cations can pass non-selectively. Both the basal level of [Ca2+]i and the Ca2+ response to membrane depolarization are greater in cells expressing mutant α-synuclein. The membrane permeable Ca2+ chelator BAPTA-AM significantly protected the cells against oxidative stress, whereas neitherl-type (nifedipine) nor N-type (ω-conotoxin-GVIA) Ca2+ channel blockers protected the cells. These findings suggest that the high membrane ion permeability caused by mutant α-synuclein may contribute to the degeneration of neurons in PD.
- Subjects
PARKINSON'S disease; CELL membranes; DOPAMINERGIC neurons; CELL death; GENETIC mutation
- Publication
Journal of Neurochemistry, 2006, Vol 97, Issue 4, p1071
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2006.03803.x