Towards a unified model of action potential generation

迈向动作电位生成的统一模型

• 批准号: 9171321
• 负责人: Roy Ben-Shalom
• 金额: $ 5.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9171321
• 关键词: Action Potentials; Acute; Algorithms; Axon; Biological; Biophysics; Brain; Calcium Channel; Cells; Complement; Complex; Data; Development; Disease; Dopamine; Electrophysiology (science); Environment; Epilepsy; Etiology; Fever; Functional disorder; Generations; Goals; Health; Hodgkin Disease; Image; Imaging Techniques; Ion Channel; Kinetics; Light; Mammals; Modeling; Modernization; Neurons; Neuropathy; Pathway interactions; Pharmacology; Play; Potassium Channel; Preparation; Proteins; Regulation; Resolution; Role; Running; Seminal; Signal Transduction; Site; Slice; Squid; System; Testing; Time; Whole-Cell Recordings; Work; base; biophysical analysis; biophysical model; biophysical properties; density; dopamine D3 receptor; experimental study; hippocampal pyramidal neuron; improved; nervous system disorder; neuronal excitability; neuroregulation; novel; public health relevance; simulation; supercomputer; two-photon; voltage; voltage clamp; voltage gated channel

 DESCRIPTION (provided by applicant): The axon initial segment has a unique composition of ion channels that enables action potential initiation. Studying the biophysical properties of this compartment is crucial for understanding neuronal excitability and associated neuronal disorders, including epilepsy. Recently, we found that Ca channels are clustered in the initial segment. Our lab showed that those channels play a critical role in neuronal excitability, and that these channels are subject to dopamine neuromodulation. Modern models of the initial segment includes realistic distributions of Na and K channels, but do not include Ca channels. Here, our goal is to utilize electrophysiological and imaging techniques, both in acute brain slice and heterologous systems, to understand the role of Ca channels in action potential initiation, and to determine how dopaminergic signaling alters the biophysical properties of axonal Ca channels. These data will be incorporated into new models of axon initial segment excitability using novel, GPU-based simulation environments.

 描述（由申请方提供）：轴突起始段具有独特的离子通道组成，可启动动作电位。研究这一区室的生物物理特性对于理解神经元兴奋性和相关的神经元疾病（包括癫痫）至关重要。最近，我们发现钙通道聚集在初始段。我们的实验室表明，这些通道在神经元兴奋性中发挥着关键作用，并且这些通道受到多巴胺神经调节。初始段的现代模型包括Na和K通道的实际分布，但不包括Ca通道。在这里，我们的目标是在急性脑切片中利用电生理和成像技术 和异源系统，了解钙通道在动作电位启动中的作用，并确定多巴胺能信号传导如何改变轴突钙通道的生物物理特性。这些数据将被纳入轴突初始段兴奋性的新模型，使用新的，基于GPU的仿真环境。