Slowly Inactivating K+ Channels in Neocortical Pyramidal Cells

缓慢失活新皮质锥体细胞中的 K 通道

基本信息

批准号：
8096622
负责人：
Robert C Foehring
金额：
$ 31.3万
依托单位：
UNIVERSITY OF TENNESSEE HEALTH SCI CTR
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-03-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8096622
关键词：
Action Potentials Acute Anesthetics Apical Apoptosis Ataxia Behavior Cell physiology Cells Data Dendrites Development Disease Distal Drug abuse Epilepsy Functional disorder Funding Genetic Health Individual Ion Channel Ischemia Knock-out Knowledge Kv2.1 channel Lead Mediator of activation protein Membrane Molecular Neurons Pattern Potassium Potassium Channel Preparation Process Property Pyramidal Cells Rattus Reverse Transcriptase Polymerase Chain Reaction Role Schizophrenia Seizures Serotonin Signal Pathway Site Slice Somatosensory Cortex Synapses Synaptic Transmission System Techniques Testing Time Training Voltage-Gated Potassium Channel Whole-Cell Recordings Work cell type hippocampal pyramidal neuron immunocytochemistry in vivo neocortical neuronal cell body neuronal excitability neuronal patterning receptor receptor coupling relating to nervous system response voltage

项目摘要

DESCRIPTION (provided by applicant): Voltage-gated potassium channels control neuronal excitability and sculpt patterns of neuronal activity. Molecular studies have documented the diversity of subunits and revealed some of the rules governing the association of subunit types. Studies in expression systems have demonstrated the biophysical and pharmacological properties of defined channel types. In contrast, relatively little is known about the composition or functional division of labor of potassium channels in native membranes. We concentrate on the influence of somatic and dendritic Kv channels on computations made by neocortical pyramidal cells to convert synaptic inputs into spike trains. The average rate and timing of action potentials are integral to the functions of neocortical pyramidal cells. In particular, temporal selectivity of pyramidal cells facilitates rhythmic and synchronous activity in cortical circuits, which in turn is important in attentional and perceptual processes in vivo and underlies spread of seizures in epileptic cortex. Most synaptic inputs to pyramidal cells are to dendrites, thus dendritic ion channels are interposed between inputs and the site of spike initiation. Nonlinearities due to activation of a dendritic Ca2+dependent spike initiation zone can lead to intrinsic burst firing in pyramidal cells, which makes synaptic transmission more reliable and facilitates oscillatory behavior. Our previous work indicates that neocortical pyramidal cells express several slowly-inactivating potassium currents. We will concentrate on Kv1 and Kv2 subunits and characterize single channel properties, test functional hypotheses concerning dendritic vs. somatic distribution of channel subunits, and test for a role of Kv2 channels in filtering responses to noisy inputs (to mimic background synaptic inputs). These data are essential for understanding how pyramidal cells process synaptic inputs in health and disease. Abnormalities of Kv1 channels have been implicated in epilepsy and ataxia. Kv2 channels are targets of anesthetic agents, regulators of excitability in many neuronal and nonneuronal cell types, and mediators of apoptosis in cortical neurons. In addition, the distribution and properties of Kv2.1 channels are altered by seizures and ischemia. PUBLIC HEALTH RELEVANCE: These basic studies test how specific potassium channel subunits influence dendritic and somatic computations made by neocortical pyramidal cells to convert inputs into spike trains. These data are essential for understanding how pyramidal cells process synaptic inputs in health and disease.

描述（由申请人提供）：电压门控钾通道控制神经元活动的神经元兴奋性和雕刻模式。分子研究记录了亚基的多样性，并揭示了有关亚基类型关联的一些规则。表达系统中的研究表明，定义的通道类型的生物物理和药理特性。相比之下，对天然膜中钾通道的劳动力的组成或功能划分相对较少。我们专注于体细胞和树突状KV通道对新皮层锥体细胞进行的计算，以将突触输入转化为尖峰列。动作电位的平均速率和时间是新皮质锥体细胞功能不可或缺的一部分。特别是，锥体细胞的时间选择性促进了皮质回路中的节奏和同步活性，这反过来在体内的注意力和感知过程中很重要，并且在癫痫皮质中癫痫发作的基础传播。大多数对锥体细胞的突触输入是对树突的，因此树突离子通道在输入和峰值起始位置之间插入。由于树突状Ca2+依赖性尖峰起始区的激活而引起的非线性会导致金字塔细胞中的内在爆发发射，从而使突触传递更加可靠并促进振荡行为。我们以前的工作表明，新皮层锥体细胞表达了几种缓慢灭活的钾电流。我们将专注于KV1和KV2亚基，并表征单个通道特性，关于树突状与通道亚基的体细胞分布的测试功能假设，并测试KV2通道在过滤对嘈杂输入的响应中的作用（以模拟背景突触输入）。这些数据对于了解锥体细胞如何处理健康和疾病中的突触输入至关重要。 KV1通道的异常已与癫痫和共济失调有关。 KV2通道是麻醉剂的靶标，许多神经元和非神经元细胞类型的兴奋性调节剂，以及皮质神经元中凋亡的介体。另外，Kv2.1通道的分布和特性会因癫痫发作和缺血而改变。公共卫生相关性：这些基础研究测试了特定的钾通道亚基如何影响新皮层金字塔细胞进行的树突状和躯体计算，以将输入转化为尖峰火车。这些数据对于了解锥体细胞如何处理健康和疾病中的突触输入至关重要。