Polyamine block of inwardly-rectifying potassium channels

点击翻译按钮获取中文摘要

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.