Plasma membrane ion permeability induced by mutant α-synuclein contributes to the degeneration of neural cells

Katsutoshi Furukawa, Michiko Matsuzaki-Kobayashi, Takafumi Hasegawa, Akio Kikuchi, Naoto Sugeno, Yasuto Itoyama, Yue Wang, Pamela J. Yao, Ittai Bushlin, Atsushi Takeda

Research output: Contribution to journalArticle

84 Citations (Scopus)

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 neither l-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.

Original languageEnglish
Pages (from-to)1071-1077
Number of pages7
JournalJournal of Neurochemistry
Volume97
Issue number4
DOIs
Publication statusPublished - 2006 May

Keywords

  • Apoptosis
  • Calcium
  • Ion channel
  • Parkinson's disease
  • Plasma membrane
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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