Plasma membrane ion permeability induced by mutant α-synuclein contributes to the degeneration of neural cells
Article first published online: 5 APR 2006
Journal of Neurochemistry
Volume 97, Issue 4, pages 1071–1077, May 2006
How to Cite
Furukawa, K., Matsuzaki-Kobayashi, M., Hasegawa, T., Kikuchi, A., Sugeno, N., Itoyama, Y., Wang, Y., Yao, P. J., Bushlin, I. and Takeda, A. (2006), Plasma membrane ion permeability induced by mutant α-synuclein contributes to the degeneration of neural cells. Journal of Neurochemistry, 97: 1071–1077. doi: 10.1111/j.1471-4159.2006.03803.x
- Issue published online: 5 APR 2006
- Article first published online: 5 APR 2006
- Received July 1, 2005; revised manuscript received December 9, 2005; accepted January 22, 2006.
- ion channel;
- Parkinson's disease;
- plasma membrane
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.