Slowly Inactivating K+ Channels in Pyramidal Neurons

缓慢失活锥体神经元中的 K 通道

• 批准号: 6844743
• 负责人: Robert C Foehring
• 金额: $ 31.05万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6844743
• 关键词: electrophysiology; epilepsy; gene expression; genetically modified animals; immunocytochemistry; infrared microscopy; laboratory mouse; laboratory rat; neocortex; neurons; neurophysiology; polymerase chain reaction; potassium channel; pyramidal cells; somesthetic sensory cortex; synapses; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): Voltage-gated potassium currents play a crucial role in controlling neuronal excitability and sculpting patterns of neuronal activity. Consistent with these roles, K+ channels are exceptionally diverse. This diversity comes in part, from multiple genes, post-translational mechanisms, and heteromeric co-assembly of subunits. Recent molecular work has documented the diversity of subunits and has 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. Relatively little is known about the composition of K+ channels in native membranes. The division of labor between the various K+ channel types in individual cells is also incompletely understood. Firing of regular-spiking (RS) pyramidal neurons in neocortex is characterized by relatively broad spikes, modest fAHPs, complex subthreshold integration, and rhythmic, repetitive firing with spike-frequency adaptation (SFA). In vivo studies indicate that the characteristic firing pattern of RS cells is integral to their functions in local circuit processing. Previous work by others and ourselves indicate that neocortical pyramidal cells express several K+ currents which regulate excitability. In particular, there is a diversity of slowly inactivating currents. This proposal is to (1) characterize the slowly-inactivating voltage-gated K+ currents and channel subunits in layer II/III pyramidal neurons from rat somatosensory cortex, (2) determine the relationship between particular channel subunits and macroscopic K+ currents, and (3) determine the mechanisms by which voltage-gated K+ currents regulate the RS firing pattern. These data are essential for understanding how pyramidal cells integrate synaptic inputs into spike trains, a process underlying cortical output. This work will also provide insights into abnormal cortical excitability and disease processes, such as epilepsy, as well as provide knowledge of the substrate for modulation by transmitters.

描述（由申请人提供）：电压门控钾电流在控制神经元活动的神经元兴奋性和雕刻模式中起着至关重要的作用。与这些角色一致，K+通道异常多样。这种多样性部分来自多个基因，翻译后机制和亚基的异元共组装。最近的分子工作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。关于天然膜中K+通道的组成相对鲜为人知。在单个细胞中各种K+通道类型之间的劳动分裂也未完全理解。新皮层中的常规尖刺（RS）锥体神经元的射击的特征是相对较宽的尖峰，适度的FAHP，复杂的亚阈值集成以及有节奏的，具有峰值频率适应性的节奏，重复的放电（SFA）。体内研究表明，RS细胞的特征发射模式是其在局部电路处理中的功能不可或缺的。他人和我们自己的先前工作表明，新皮层锥体细胞表达了几种调节兴奋性的K+电流。特别是，缓慢失活的电流多样性。 This proposal is to (1) characterize the slowly-inactivating voltage-gated K+ currents and channel subunits in layer II/III pyramidal neurons from rat somatosensory cortex, (2) determine the relationship between particular channel subunits and macroscopic K+ currents, and (3) determine the mechanisms by which voltage-gated K+ currents regulate the RS firing pattern.这些数据对于理解锥体细胞如何将突触输入整合到尖峰列车中是必不可少的，这是皮层输出的基础过程。这项工作还将提供有关皮质兴奋性异常和疾病过程（例如癫痫）的见解，并提供了通过发射器调节的底物知识。