Characterization of an alternative current pathway (sigma-pore) through voltage-gated potassium channels

通过电压门控钾通道的替代电流通路（西格玛孔）的表征

• 批准号: 241491293
• 负责人: Professor Dr. Stephan Grissmer
• 金额: --
• 依托单位: Institut für Angewandte Physiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/241491293?language=en
• 关键词: Characterization; alternative; current; pathway; sigma

In the background of the mammalian specific hKv1.3 potassium channel in a channel mutant (hKv1.3_V388C) an unexpected current could be recorded in my laboratories. This current did neither flow through the central alpha-pore nor through the omega-pore in the voltage-sensing-domain. I would like to find out, whether this current pathway, that we named sigma-pore, indeed runs behind the alpha-pore or whether this current pathway is still through the alpha-pore with new, modified alpha-pore characteristics (selectivity, activation, deactivation, inactivation). In addition, I would like to test, whether other potassium channels (hKv1.2, hERG) are also able to generate current through a sigma-pore. The results of these planned experiments should increase our knowledge of the functional channel structure for potassium channels and enable the rational design of specific channel modulators, being able to block current through the sigma-pore. This is important since mutations in other potassium channels (KCNQ1, hERG, Kir2.1) in close proximity of the homologue position 388 in hKv1.3 are associated with different channelopathies.

在通道突变体 (hKv1.3_V388C) 中哺乳动物特异性 hKv1.3 钾通道的背景下，我的实验室可能会记录到意想不到的电流。该电流既不流经中央 α 孔，也不流经电压传感域中的 omega 孔。我想知道，我们称之为 sigma-pore 的当前路径是否确实在 α-pore 后面运行，或者当前路径是否仍然通过具有新的、修改的 α-pore 特性（选择性、激活、失活、失活）的 α-pore。另外，我想测试一下，其他钾通道（hKv1.2、hERG）是否也能够通过西格玛孔产生电流。这些计划实验的结果应该会增加我们对钾通道功能通道结构的了解，并能够合理设计特定的通道调节剂，能够阻止电流通过西格玛孔。这很重要，因为紧邻 hKv1.3 中同源物位置 388 的其他钾通道（KCNQ1、hERG、Kir2.1）中的突变与不同的通道病相关。