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Influence of erg potassium channels on rhythmic activity of cerebellar Purkinje cells and motor control of movements

尔格钾通道对小脑浦肯野细胞节律活动和运动控制的影响

基本信息

批准号：
212105264
负责人：
Professor Dr. Jürgen R. Schwarz
金额：
--
依托单位：
Fachrichtung Physiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2012
资助国家：
德国
起止时间：
2011-12-31 至 2015-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/212105264?language=en
关键词：
Influence erg potassium channels rhythmic

项目摘要

The aim of the previously approved grant (Schw 292/16-1) is to test the hypothesis, whether the activity of erg K channels in cerebellar Purkinje cells is directly involved in the motor control of balance and of the coordination of body movements. To achieve this goal we want to knock-down erg K channels in Purkinje cells of adult mice by viral transduction of siRNA. We want to investigate at the cellular level whether loss of erg K channels in Purkinje cells influences neuronal activity, like burst activity, and at the level of behavior we want to test the influence of erg K channel loss on motor behavior. The present grant was approved in January 2012. Since then we have performed successfully experiments which showed that in Purkinje cells erg1a channels are presumably mediating the native erg K channels. This result was obtained by quantitative RT-PCR and by performing electrophysiological experiments in which we used erg subunit sensitive toxins. This part of the project has been successfully published in October 2013 in The Journal of Neuroscience. In addition, we have tested two siRNA constructs which effectively inhibit erg1a expression in HEK cells expressing erg1a K channels by about 85%, we have constructed the main part of the viral vector and have established organotypic slices of the cerebellum as a test preparation. We need one additional year to complete the construction and testing of the viral vector, to perform the stereotaxic application of the viral solution to the cerebellum and to perform the investigation of the motor behavior of mice lacking the erg1 K channels in Purkinje cells.

先前批准的拨款（Schw 292/16-1）的目的是检验这一假设，即小脑浦肯野细胞中erg K通道的活性是否直接参与平衡和身体运动协调的运动控制。为了实现这一目标，我们希望通过siRNA的病毒转导来敲低成年小鼠浦肯野细胞中的erg K通道。我们想在细胞水平上研究浦肯野细胞中erg K通道的丢失是否会影响神经元的活动，如爆发活动，在行为水平上，我们想测试erg K通道丢失对运动行为的影响。目前的赠款于2012年1月获得批准。从那时起，我们已经成功地进行了实验，表明在浦肯野细胞erg 1a通道可能介导的天然erg K通道。这一结果是通过定量RT-PCR和进行电生理实验，其中我们使用erg亚基敏感毒素。该项目的这一部分已于2013年10月成功发表在《神经科学杂志》上。此外，我们已经测试了两种siRNA构建体，其有效地抑制表达erg 1a K通道的HEK细胞中的erg 1a表达约85%，我们已经构建了病毒载体的主要部分，并建立了小脑的器官型切片作为测试制剂。我们还需要一年的时间来完成病毒载体的构建和测试，将病毒溶液立体定位应用于小脑，并对浦肯野细胞中缺乏erg 1 K通道的小鼠的运动行为进行研究。