K+ channels in fast-spiking cell synaptic transmission

快速尖峰细胞突触传递中的 K 通道

• 批准号: 6992656
• 负责人: ETHAN M GOLDBERG
• 金额: $ 4.41万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992656
• 关键词: cognition; electrophysiology; epilepsy; gamma aminobutyrate; genetically modified animals; laboratory mouse; neural transmission; neuropathology; potassium channel; potassium ion; predoctoral investigator; voltage /patch clamp

DESCRIPTION (provided by applicant): Epilepsy affects 1-2% of the world's population. Given the role of voltage-gated ion channels in the regulation of neuronal excitability, there is general agreement that ion channels are involved in the pathogenesis of at least some forms of this disease. In fact, various types of epilepsy are due to mutation of genes that encode for components of voltage-gated channels selective for potassium (K+). Mice defective in the voltage-gated K+ channels Kv3.1 and Kv3.2 are epileptic, likely due to impaired cortical inhibition. This project seeks to study the role of Kv3.1/Kv3.2 in the properties of fast-spiking GABAergic interneurons (FS cells) - where these channels are specifically expressed - using dual whole-cell patch clamp recordings in the neocortex of mouse. Of particular interest are the roles of Kv3.1 and Kv3.2 in (1) neurotransmission at the FS cell terminal, and (2) the network behavior of interconnected FS cells. This project will explore the dynamics of GABA release at the FS cell terminal and its derangement in Kv3.1/3.2 knockout mice, and the disruption of synchronous FS cell behavior in these mice. This work may have implications for normal cognitive functions as well as neuropathology involving the GABAergic system, including epilepsy.

描述（由申请人提供）： 癫痫会影响世界人口的1-2％。鉴于电压门控离子通道在调节神经元兴奋性中的作用，人们普遍认为离子通道参与至少某些形式的该疾病的发病机理。实际上，各种类型的癫痫症是由于编码钾（K+）选择性的基因的突变所致。电压门控的K+通道中有缺陷的小鼠Kv3.1和Kv3.2是癫痫病，可能导致皮质抑制受损。该项目旨在研究Kv3.1/kv3.2在快速刺激的GABA能中间神经元（FS细胞）中的作用 - 这些通道是特异性表达的 - 使用小鼠新皮层中的双电池贴剂记录。特别有趣的是Kv3.1和Kv3.2在FS细胞末端（1）神经传递中的作用，以及（2）互连FS细胞的网络行为。该项目将探索FS细胞端子上GABA释放的动力学及其在KV3.1/3.2敲除小鼠中的扰动，并破坏这些小鼠同步FS细胞行为。这项工作可能对正常的认知功能以及涉及包括癫痫在内的GABA能系统的神经病理学有影响。