The activation mechanisms of Kv and Nav channels

描述(申请人提供)：电压依赖性离子通道激活机制的问题近年来一直是一个有争议的领域。传统的激活模型主要基于对Shaker钾通道的研究中的功能和生化数据。虽然功能数据对于理解电压依赖的Kv通道生理学至关重要，但要完全理解通道激活背后的机制，则需要结构数据。R·麦金农博士的实验室发表了电压依赖性钾通道KvAP的两种高分辨率晶体结构。有了这些晶体结构，麦金农博士的实验室发布了一种新的通道激活模型--桨模型，该模型与传统模型有许多不同。我的建议旨在通过基于Tb(Tb3)的发光共振能量转移(LRET)来研究KvAP和NaChBac的拓扑结构和激活机制，从而确定哪个模型最适合于原核离子通道KvAP和NaChBac。电压依赖性离子通道是兴奋性细胞疾病的根本原因。因此，了解它们的作用机制对于了解和治疗这种疾病是至关重要的。

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.