Role of EAG K+ Channels in Cortical Function

EAG K 通道在皮质功能中的作用

• 批准号: 0314645
• 负责人: Bernardo Rudy
• 金额: $ 56万
• 依托单位: New York University Medical Center
• 依托单位国家: 美国
• 项目类别: Continuing grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0314645&HistoricalAwards=false
• 关键词: Role; EAG; K+; Channels; Cortical

The action potential is the universal signal in the nervous system throughout the animal kingdom. Action potentials are very similar in different parts of the nervous system and between different animals. Information is instead encoded in the frequency and temporal pattern of series of action potentials. Several factors contribute to generating these patterns. Among these, the diversity of ion channels carrying, potassium (K+) ions, known as K+ channels, is one of the main factors contributing to the shaping of neural signals. A large number of new K+ channels have been discovered recently through genetic molecular analysis. Additional discoveries can be expected as the full sequence of the genomes of several animals becomes known. A major task of future research is to understand the physiological roles of these channels. This project will study a new K+ channel gene family, known as EAG, recently identified and cloned from flies and mammals. The products of EAG genes have been introduced into model cells, where they result in the formation of K+ channels with unique and intriguing functional properties. The task is to determine if they have the same properties in their native environment in the brain and to unravel their roles in neural signaling. To discover the functional roles of EAG channels, experiments are designed to explore which brain cells normally contain the products of the genes encoding these channels. Electrophysiological techniques are then used to study their properties in native cells, and their role in shaping neuronal signals. Previous investigations in the applicant's laboratory have shown that several EAG gene products are particularly prominent in neurons in the cerebral cortex, and their unique distributions suggest that EAG channels play specific roles in particular cortical circuits. This project will test the hypothesis that EAG channels have crucial functions in regulating the state of excitability of specific cortical neurons, including determining whether or not sensory information enters the cerebral cortex and hence in modulating states of consciousness. This study will contribute to the unraveling of the function of novel K+ channel genes and advance our understanding of the mechanisms by which the brain processes information. This study will contribute to the development of methods to discover the roles of newly found genes, and multidisciplinary training to a graduate student.

动作电位是动物界神经系统的普遍信号。动作电位在神经系统的不同部分和不同动物之间非常相似。相反，信息被编码在一系列动作电位的频率和时间模式中。有几个因素促成了这些模式的产生。其中，携带钾（K+）离子的离子通道（称为K+通道）的多样性是促成神经信号成形的主要因素之一。 近年来，通过遗传分子分析发现了大量新的钾离子通道。随着几种动物基因组的完整序列被发现，可以预期会有更多的发现。未来研究的主要任务是了解这些通道的生理作用。 该项目将研究一个新的K+通道基因家族，称为EAG，最近从苍蝇和哺乳动物中鉴定和克隆。 EAG基因的产物已被引入到模型细胞中，在那里它们导致形成具有独特和有趣的功能特性的K+通道。这项任务是确定它们在大脑中的原生环境中是否具有相同的特性，并揭示它们在神经信号中的作用。为了发现EAG通道的功能作用，实验旨在探索哪些脑细胞通常含有编码这些通道的基因的产物。然后使用电生理技术研究它们在天然细胞中的特性以及它们在塑造神经元信号中的作用。 申请人实验室的先前研究已经表明，几种EAG基因产物在大脑皮层的神经元中特别突出，并且它们独特的分布表明EAG通道在特定的皮层回路中起特定的作用。该项目将测试EAG通道在调节特定皮层神经元的兴奋性状态中具有关键功能的假设，包括确定感觉信息是否进入大脑皮层，从而调节意识状态。 本研究将有助于揭示新的K+通道基因的功能，并促进我们对大脑处理信息的机制的理解。 这项研究将有助于发现新发现基因的作用的方法的发展，以及对研究生的多学科培训。