Expression and Function of K+ channel genes in brain

K通道基因在脑中的表达和功能

基本信息

批准号：
7407393
负责人：
Bernardo Rudy
金额：
$ 37.06万
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：
1992
资助国家：
美国
起止时间：
1992-08-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7407393
关键词：
Action Potentials Acute Affect Appendix Brain Cell physiology Cells Cerebral cortex Chemicals Chromosome Pairing Code Cognitive Computer Simulation Computer information processing Condition Electrical Synapse Elements Epilepsy Fire - disasters Frequencies Funding Generations Genes Goals Interneurons Knockout Mice Knowledge Kv3.2 channel Laboratories Mediating Mental Depression Molecular Mus Mutation Names Neuraxis Neurons Neurotransmitters Norepinephrine Output Pathogenesis Pattern Pharmaceutical Preparations Phosphorylation Physiological Poison Potassium Potassium Channel Predisposition Presynaptic Terminals Process Progress Reports Property Rate Regulation Role Seizures Sensory Shapes Signal Transduction Slice Somatosensory Cortex Specificity Synapses Synaptic Transmission Testing Therapeutic Training gamma-Aminobutyric Acid hippocampal pyramidal neuron human disease interest member neuronal cell body neuronal excitability neurotransmitter release research study synaptic depression therapeutic target tool transmission process voltage voltage gated channel

项目摘要

DESCRIPTION (provided by applicant): The long term goal of this project is to contribute to the understanding of the role of K+ channel diversity in the central nervous system (CNS). K+ channels regulate neuronal excitability. They underlie many of the differences in functional properties that characterize specific neurons, contributing to the complexity of neuronal information coding and integration. It is hypothesized that their diversity provides signaling specificity to neuronal circuits and to the actions of neurotransmitters. Mutations in genes encoding K+ channels have been found to cause epilepsy and other types of human disease. This proposal focuses on a subtype of cortical GABAergic inhibitory interrneuron known as the fast-spiking (FS) cell, named for its ability to fire sustained trains of action potentials (APs) at remarkably high frequencies. GABAergic interneurons are key components of the cerebral cortex and have essential roles in information processing, plasticity, the generation of cortical rhythms, and in the pathogenesis of seizures. Knowledge of the molecular elements responsible for FS cell function is critical for the manipulation of cortical function to understand physiological and pathophysiological conditions and to provide targets for therapeutic drugs. It has been demonstrated that K+ channels of the Kv3 subfamily contribute to the ability of FS cells to fire at high frequency and preliminary evidence shows that the same channels have a key role in the regulation of synaptic transmission from FS cell terminals. Two additional types of K+ channels have also been found at the FS cell synapse. Aim I will utilize electrophysiological recordings in acute slices from primary somatosensory cortex in mice to investigate the functions of the three types of K+ channels so far discovered at FS terminals. Immunolocalization will be used to investigate how localization within the synapse affects the roles of each type of channel. Aim II will utilize electrophysiological recordings from electrically and chemically connected FS cells to understand the role of these channels in generating synchronous activity within FS cell networks.

描述（由申请人提供）：该项目的长期目标是有助于理解K+通道多样性在中枢神经系统（CNS）中的作用。 K+通道调节神经元兴奋性。它们是表征特定神经元的功能特性的许多差异，这有助于神经元信息编码和整合的复杂性。假设它们的多样性为神经元电路和神经递质的作用提供了信号特异性。已经发现编码K+通道的基因突变会引起癫痫和其他类型的人类疾病。该提案的重点是皮质GABA能抑制性脑膜的亚型，称为快速加速器（FS）细胞，以其在较高频率下的持续持续的动作电位（AP）命名。 GABA能中间神经元是大脑皮层的关键组成部分，在信息处理，可塑性，皮质节奏的产生以及癫痫发作中具有重要作用。对负责FS细胞功能的分子元素的了解对于操纵皮质功能至关重要，以了解生理和病理生理条件并为治疗药物提供靶标。已经证明，KV3亚家族的K+通道有助于FS细胞以高频发射的能力，而初步证据表明，同一通道在调节FS Cell终端的突触传播中具有关键作用。在FS细胞突触中也发现了另外两种类型的K+通道。目的，我将利用小鼠原发性体感皮质的急性切片中的电生理记录来研究迄今为止在FS端子发现的三种类型的K+通道的功能。免疫定位将用于研究突触中的定位如何影响每种类型的通道的作用。 AIM II将利用来自电和化学连接的FS细胞的电生理记录来了解这些通道在FS细胞网络中产生同步活动中的作用。