Interaction of Subunits Regulating Resurgent Current Through Voltage Gated Na Channels

亚基通过电压门控 Na 通道调节复活电流的相互作用

• 批准号: 9755139
• 负责人: Hayley Virginia White
• 金额: $ 3.98万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755139
• 关键词: Action Potentials; Acute; Amino Acid Sequence; Ataxia; Behavior; Cells; Cerebellum; Communication; Data; Disease; Double Effect; Epilepsy; Eulenburg' s Disease; Fire - disasters; Frequencies; Genetic; Knock-out; Knockout Mice; Lead; Long QT Syndrome; Membrane Potentials; Molecular; Mus; Neurons; Paroxysmal extreme pain disorder; Peptides; Performance; Phosphorylation; Physiological; Play; Prevention; Production; Protein Engineering; Protein Isoforms; Proteins; Purkinje Cells; Recovery; Reflex action; Research Personnel; Role; Shapes; Sodium; Sodium Channel; Spinal Ganglia; System; Tail; Testing; Work; awake; bean; biophysical properties; cell type; chemotherapy induced neuropathy; extracellular; fibroblast growth factor-14; improved; in vivo; knock-down; particle; prevent; protein aminoacid sequence; relating to nervous system; transcriptome sequencing; voltage; voltage clamp

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.

项目摘要/摘要 复苏性钠电流是流经电压门控钠通道的电流，该电流在细胞复极化时流动， 从而增加了棘波之间通道的可用性，并使神经元能够高频放电。 这种高频的放电行为在生理上是有用的，就像小脑浦肯野神经元的情况一样。 和背根神经节神经元，但也可以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 详细阐述了复苏电流的生物物理特征，复苏电流的分子机制 产量仍不得而知。我们正在研究几个辅助亚基对钠通道的作用 这可能在复活洋流中起到一定作用。我们将通过执行全电池电压钳记录来实现这一点 在它们与辅助性物质相互作用的背景下，通过表达的和自然的通道的钠电流 亚基，以及研究这些蛋白质在促进体内行为方面的作用。通过澄清什么 因素是产生和调节复活电流的重要因素，我们将通过以下方式定义分子机制 哪些神经元类型会产生高频放电，这将有助于我们对神经的理解 生理和病理生理状态下的沟通。