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: 7174626
• 负责人: ETHAN M GOLDBERG
• 金额: $ 3.34万
• 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/7174626
• 关键词: Action Potentials; Affect; Agreement; Attenuated; Behavior; Calcium-Binding Proteins; Cells; Chemicals; Chromosome Pairing; Detection; Disease; Disruption; Electrical Synapse; Electroencephalography; Electrophysiology (science); Epilepsy; Exhibits; Fire - disasters; Frequencies; Gap Junctions; Gated Ion Channel; Gene Mutation; Generations; Genes; Genetic; Goals; Human; Immunohistochemistry; In Vitro; Interneurons; Ion Channel; Knock-out; Knockout Mice; Knowledge; Kv3.2 channel; Laboratories; Molecular Biology; Mus; Names; Neocortex; Neurons; Output; Parvalbumins; Pathogenesis; Pattern; Periodicity; Pharmacology; Phenotype; Population; Potassium; Potassium Channel; Presynaptic Terminals; Property; Pyramidal Cells; Reagent; Regulation; Role; Seizures; Signal Transduction; Students; Synapses; Synaptic Transmission; System; Techniques; Testing; Time; Training; Transgenic Mice; Voltage-Gated Potassium Channel; Work; cell behavior; cell cortex; cognitive function; design; enhanced green fluorescent protein; experience; gamma-Aminobutyric Acid; genetic manipulation; in vivo; interest; member; neocortical; neuronal cell body; neuronal excitability; neuropathology; neurotransmission; neurotransmitter release; patch clamp; promoter; research study; voltage; voltage gated channel

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，普遍认为离子通道参与了至少某些形式的这种疾病的发病机制。事实上，各种类型的癫痫是由于编码对钾（K+）具有选择性的电压门控通道组分的基因突变。电压门控K+通道Kv3.1和Kv3.2缺陷的小鼠是癫痫性的，可能是由于受损的皮质抑制。该项目旨在研究Kv3.1/Kv3.2在快速尖峰GABA能中间神经元（FS细胞）特性中的作用-这些通道特异性表达-使用双全细胞膜片钳记录在小鼠新皮层中。特别感兴趣的是Kv3.1和Kv3.2在（1）FS细胞末端的神经传递和（2）互连FS细胞的网络行为中的作用。本项目将探讨Kv3.1/3.2基因敲除小鼠FS细胞末端GABA释放的动力学及其紊乱，以及这些小鼠同步FS细胞行为的破坏。这项工作可能对正常的认知功能以及涉及GABA能系统的神经病理学（包括癫痫）有影响。