The activation mechanisms of Kv and Nav channels

Kv和Nav通道的激活机制

• 批准号: 7104376
• 负责人: JESSICA L RICHARDSON
• 金额: $ 2.96万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-05 至 2008-07-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104376
• 关键词: antibiotics; fluorescence resonance energy transfer; liposomes; membrane potentials; potassium channel; predoctoral investigator; protein purification; protein reconstitution; protein structure function; protein transport; site directed mutagenesis; sodium channel; voltage gated channel

DESCRIPTION (provided by applicant): The question of the mechanism of voltage dependent ion channel activation has been a controversial area of interest in recent years. Traditional models of activation have been based primarily on functional and biochemical data from studies on the Shaker potassium channel. While functional data are critical for the understanding of voltage dependent Kv channel physiology, structural data are needed to fully understand the mechanism behind channel activation. The laboratory of Dr. R. MacKinnon published two high resolution crystal structures of the voltage dependent potassium channel, KvAP. With these crystal structures, Dr. MacKinnon's lab published a new model of channel activation, the paddle model, that has many differences from the traditional model. My proposal aims to determine which model best fits the prokaryotic ion channels KvAP and NaChBac by using terbium (Tb3+)-based luminescence resonance energy transfer (LRET) to study the topology and mechanism of activation of KvAP and NaChBac. Voltage dependent ion channels are the underlying causes of diseases in excitatory cells. Thus, it is critical to understand their functional mechanisms in order to understand and treat such disease.

描述（由申请人提供）：近年来，电压依赖性通道激活机制的问题一直是一个有争议的领域。传统的激活模型主要基于对沙克钾通道的功能和生化数据的研究。虽然功能数据对于理解电压相关的Kv通道生理学至关重要，但要充分理解通道激活背后的机制，还需要结构数据。R. MacKinnon博士的实验室发表了两个高分辨率的电压依赖性钾通道（KvAP）晶体结构。有了这些晶体结构，麦金农博士的实验室发表了一种新的通道激活模型——桨形模型，它与传统模型有很多不同。我的提议旨在通过利用铽（Tb3+）基发光共振能量转移（LRET）研究KvAP和NaChBac的拓扑结构和激活机制，确定哪种模型最适合原核离子通道KvAP和NaChBac。电压依赖性离子通道是兴奋性细胞疾病的潜在原因。因此，了解它们的功能机制对于了解和治疗此类疾病至关重要。