Polyamine block of inwardly-rectifying potassium channels

多胺阻断内向整流钾通道

• 批准号: 374531-2009
• 负责人: Kurata, Harley
• 金额: $ 2.2万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528569
• 关键词: Polyamine; block; inwardly; rectifying; potassium

Inwardly-rectifying potassium (Kir) channels are a class of protein named for the unique electrical property of inward rectification. This refers to the ability to allow potassium ions to flow preferentially into cells, rather than out of cells, and is caused by voltage-dependent block of these channels by a class of small organic molecules called polyamines, found in virtually all cells. When cells are at rest, Kir channels are open, and potassium ions flow freely. However, at membrane voltages where potassium is driven out of the cell, polyamines enter and block the Kir channel pore, preventing movement of potassium through the channel. This process is rapid and dynamic, occuring with every beat of the heart and every muscle contraction, and is vital to the appropriate function of many excitable cells. The proposed research will examine the fundamental details of polyamine-regulated inward rectification, identifying components of the channel that interact with the blocker, and mechanisms that underlie the voltage-dependence of interaction between polyamines and Kir channels. It is anticipated that the results of this research will enhance our understanding of basic mechanisms critical to cellular excitability, and will also offer new and general insights into principles of ion channel blockade.

内向整流钾（Kir）通道是一类以内向整流的独特电特性命名的蛋白质。这是指允许钾离子优先流入细胞而不是流出细胞的能力，并且是由一类称为多胺的小有机分子对这些通道的电压依赖性阻断引起的，几乎在所有细胞中都存在。当细胞处于静止状态时，Kir通道打开，钾离子自由流动。然而，在钾被赶出细胞的膜电压下，多胺进入并阻断Kir通道孔，阻止钾通过通道的移动。这个过程是快速和动态的，伴随着心脏的每一次跳动和肌肉的每一次收缩，并且对许多可兴奋细胞的适当功能至关重要。拟议的研究将研究多胺调节的内向整流的基本细节，确定与阻滞剂相互作用的通道成分，以及多胺和Kir通道之间相互作用的电压依赖性机制。预计这项研究的结果将提高我们对细胞兴奋性的基本机制的理解，并将为离子通道阻滞的原理提供新的和一般的见解。