期刊
ENEURO
卷 8, 期 1, 页码 -出版社
SOC NEUROSCIENCE
DOI: 10.1523/ENEURO.0330-20.2020
关键词
alpha-synuclein; dopamine; electrophysiology; KATP; patch clamp; substantia nigra
资金
- Biotechnology and Biological Science Research Council-funded PhD Studentship
- Engineering and Physical Sciences Research Council-funded PhD Studentship
The study indicates that oligomeric alpha-synuclein plays a significant role in Parkinson's disease, leading to functional impairment of dopaminergic neurons. Preincubation with the ATP-sensitive K+ channel inhibitor glibenclamide can effectively reduce the impact of alpha-syn aggregates.
Dopaminergic neurons (DNs) in the substantia nigra pars compacta (SNpc) form an important part of the basal ganglia circuitry, playing key roles in movement initiation and coordination. A hallmark of Parkinson's disease (PD) is the degeneration of these SNpc DNs leading to akinesia, bradykinesia and tremor. There is gathering evidence that oligomeric alpha-synuclein (alpha-syn) is one of the major pathologic species in PD, with its deposition in Lewy bodies (LBs) closely correlated with disease progression. However, the precise mechanisms underlying the effects of oligomeric alpha-syn on DN function have yet to be fully defined. Here, we have combined electrophysiological recording and detailed analysis to characterize the time-dependent effects of alpha-syn aggregates (consisting of oligomers and possibly small fibrils) on the properties of SNpc DNs. The introduction of alpha-syn aggregates into single DNs via the patch electrode significantly reduced both the input resistance and the firing rate without changing the membrane potential. These effects occurred after 8-16 min of dialysis but did not occur with the monomeric form of alpha-syn. The effects of alpha-syn aggregates could be significantly reduced by preincubation with the ATP-sensitive K+ channel (KATP) inhibitor glibenclamide. These data suggest that accumulation of alpha-syn aggregates in DNs may chronically activate KATP channels leading to a significant loss of excitability and dopamine release.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据