Regulation of Voltage-Gated Potassium Channels: X-ray Structures of Cytosolic Components of the BK nd Kv Families

本研究将探讨离子通道门控（开启）的各个方面。离子通道是穿透细胞膜的专门小孔，促进离子或带电原子在细胞膜上的运输。离子从一边流向另一边的流动可以作为电流来测量。离子通过的孔或通道在区域上变窄，形成了一个死胡同或门，禁止通过。栅极由外部因素控制，例如某些分子（配体）的结合，或者在电压依赖性离子通道的情况下，对膜施加电压。这种扰动使孔洞变宽，足以允许传导。电压门控钾通道专门运输钾离子。它们分为多种类型，通常与细胞内和膜结合部分形成大型复合物。对于某些类型，已知来自细胞内化学过程的线索调节电兴奋性，利用细胞内结构域将信息传递到膜上。在其他国家，这种情况是否会发生以及如何发生尚不清楚。我们的工作将集中在Kv和BK两个对比系统中探索这一主题。Kv通道随电压打开，而BK通道的激活需要电压和中等水平的细胞内钙。x射线晶体学将用于生成所选钾通道成分的精确三维图像，使我们能够可视化调节过程中的离散步骤。钾离子通道对生命至关重要。它们影响我们神经冲动的传递，因此是中枢神经系统活动的基础。这项研究将帮助我们了解控制它们的因素。

This research will investigate aspects of ion channel gating (opening). Ion channels are specialised pores perforating cell membranes that facilitate transport of ions, or charged atoms, across its breadth. The flow of ions from one side to another is measurable as an electrical current. The pore, or channel, through which ions pass narrows in regions, creating an impasse, or gate , prohibiting passage. The gate is controlled by external factors, such as the binding of certain molecules (ligands), or, in the case of voltage-dependent ion channels, the application of a voltage to the membrane. Such perturbations widen the pore sufficiently to permit conduction. Voltage-gated potassium channels specifically transport potassium ions. They fall into multiple categories, and generally form large complexes with intracellular, as well as membrane-bound, portions. For some types, cues from intracellular chemical processes are known to regulate electrical excitability, using the intracellular domains to transfer information to the membrane. In others it is not clear if and how this might happen. Our efforts will focus on exploring this theme in two contrasting systems, Kv and BK channels. Kv channels open in response to voltage, whereas activation of BK channels requires both voltage and moderate levels of intracellular calcium. X-ray crystallography will be used to generate accurate three-dimensional images of selected potassium channel components, allowing us to visualise discrete steps in the regulation processes. Potassium channels are essential for life. They effect transmission of our nerve impulses, and are thus fundamental to central nervous system activity. This research will help us to understand the factors that control them.