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Potassium channel dysfunction and depolarized resting membrane potential in a cell model of SCA3

Item Type:Article
Title:Potassium channel dysfunction and depolarized resting membrane potential in a cell model of SCA3
Creators Name:Jeub, M. and Herbst, M. and Spauschus, A. and Fleischer, H. and Klockgether, T. and Wuellner, U. and Evert, B.O.
Abstract:Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant inherited neurodegenerative disease caused by the expansion of a polyglutamine repeat within the disease protein, ataxin-3. There is growing evidence that neuronal electrophysiological properties are altered in a variety of polyglutamine diseases such as Huntington's disease and SCA1 and that these alterations may contribute to disturbances of neuronal function prior to neurodegeneration. To elucidate possible electrophysiological changes in SCA3, we generated a stable PC12 cell model with inducible expression of normal and mutant human full-length ataxin-3 and analyzed the electrophysiological properties after induction of the recombinant ataxin-3 expression. Neuronally differentiated PC12 cells expressing the expanded form of ataxin-3 showed significantly decreased viabilities and developed ultrastructural changes resembling human SCA3. Prior to neuronal cell death, we found a significant reduction of the resting membrane potential and a hyperpolarizing shift of the activation curve of the delayed rectifier potassium current. These findings indicate that electrophysiological properties are altered in mutant ataxin-3 expressing neuronal cells and may contribute to neuronal dysfunction in SCA3.
Keywords:SCA3, Polyglutamine, PC12, Resting membrane potential, Potassium channel, Neuronal dysfunction, Electrophysiological dysfunction, Animals, Rats
Source:Exp Neurol
Page Range:182-192
Date:1 September 2006
Official Publication:https://doi.org/10.1016/j.expneurol.2006.03.029
PubMed:View item in PubMed

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