Understanding the mechanisms of ion conduction and drug action in voltage gated sodium channels

了解电压门控钠通道中离子传导和药物作用的机制

• 批准号: FT130100781
• 负责人: Prof Ben Corry
• 金额: $ 49.16万
• 依托单位: The Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: ARC Future Fellowships
• 财政年份: 2014
• 资助国家: 澳大利亚
• 起止时间: 2014-02-10 至 2020-09-22
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/FT130100781
• 关键词: Understanding; mechanisms; ion; conduction; drug

Voltage-gated sodium channels initiate electrical impulses in nerve and muscle and are the target of many local anaesthetic, anti-epileptic and anti-arrythmic drugs. The publication of atomic resolution structures of homologous proteins from bacteria in the last 18 months has now made it possible to gain a detailed understanding of how these channels work, and how they are influenced by drugs. This project aims to determine the basis of ion permeation and selectivity in the channels and explain the mechanisms of action for a number of common drugs. This will provide a foundation for future drug development to target specific channels for improved treatment of epilepsy, chronic pain and arrythmias.

电压门控钠通道在神经和肌肉中启动电脉冲，是许多局部麻醉、抗癫痫和抗心律失常药物的靶点。过去18个月发表的细菌同源蛋白质的原子分辨结构现在使人们有可能详细了解这些通道是如何工作的，以及它们是如何受到药物的影响的。该项目旨在确定离子在通道中的渗透和选择性的基础，并解释一些常见药物的作用机制。这将为未来针对特定渠道的药物开发提供基础，以改善癫痫、慢性疼痛和心律失常的治疗。