Interaction of Subunits Regulating Resurgent Current Through Voltage Gated Na Channels

项目总结/摘要 复苏Na电流是通过电压门控Na通道的电流，其在细胞复极化时流动， 从而导致尖峰之间的通道的可用性增加，并且使得能够实现神经元的高频放电。 这种高频放电行为在生理上是有用的，如小脑浦肯野神经元的情况 和背根神经节神经元，但也可导致几种病理生理状态，包括共济失调， 癫痫、阵发性极度疼痛障碍和长QT综合征。虽然许多研究都描述了 详细介绍了复活电流的生物物理特征，复活电流的分子机制 生产仍然未知。我们正在研究几个辅助亚单位的钠通道的作用 这可能在电流恢复中起作用。我们将通过进行全细胞电压钳记录来做到这一点 Na电流通过表达和天然通道，在它们与辅助细胞相互作用的背景下， 亚基，以及检查这些蛋白质在体内行为中的作用。通过阐明什么 因素对于产生和调节复苏电流是重要的，我们将通过以下方式定义分子机制： 许多神经元类型都会产生高频放电，这将有助于我们对神经元的理解 在生理和病理生理状态下的沟通。

Project Summary/Abstract Resurgent Na current is current through voltage-gated Na channels that flows upon repolarization of the cell, leading to increased availability of channels between spikes, and enabling high frequency firing of neurons. This high frequency firing behavior can be useful physiologically, as in the case of cerebellar Purkinje neurons and dorsal root ganglion neurons, but can also lead to several pathophysiological states, including ataxia, epilepsy, paroxysmal extreme pain disorder, and long QT syndrome. While many studies have described the biophysical characteristics of resurgent current in detail, the molecular mechanism of resurgent current production remains unknown. We are investigating the roles of several auxiliary subunits to the Na channel which may play a role in resurgent current. We will do this by performing whole-cell voltage clamp recordings of Na current through both expressed and native channels, in the context of their interaction with auxiliary subunits, as well as examining these proteins’ roles in contributing to behavior in vivo. By elucidating what factors are important for producing and modulating resurgent current, we will define a molecular mechanism by which many neuron types produce high frequency firing, which will help shape our understanding of neural communication in both physiological and pathophysiological states.