K+ channels in fast-spiking cell synaptic transmission

快速尖峰细胞突触传递中的 K 通道

基本信息

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
项目类别：
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

项目摘要

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）：世界上 1-2% 的人口患有癫痫症。鉴于电压门控离子通道在神经元兴奋性调节中的作用，人们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，各种类型的癫痫都是由于编码钾 (K+) 选择性电压门控通道成分的基因突变所致。电压门控 K+ 通道 Kv3.1 和 Kv3.2 有缺陷的小鼠会出现癫痫，可能是由于皮质抑制受损所致。该项目旨在利用小鼠新皮质中的双全细胞膜片钳记录，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（这些通道是在这些细胞中特异性表达的）。特别令人感兴趣的是 Kv3.1 和 Kv3.2 在 (1) FS 细胞末端的神经传递和 (2) 相互连接的 FS 细胞的网络行为中的作用。该项目将探索 Kv3.1/3.2 敲除小鼠中 FS 细胞末端 GABA 释放的动态及其紊乱，以及这些小鼠中同步 FS 细胞行为的破坏。这项工作可能对正常认知功能以及涉及 GABA 系统的神经病理学（包括癫痫）产生影响。