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

在一个通道突变体(hKv1.3_V388C)中哺乳动物特有的hKv1.3钾通道的背景中，我的实验室记录到了一种意想不到的电流。这一电流既没有流过中心α孔，也没有流过电压敏感区域中的omega孔。我想要弄清楚，这条当前的路径，我们称之为Sigma-Pole，是否真的运行在Alpha孔之后，或者这条当前路径是否仍然通过具有新的、修改的Alpha孔特征(选择性、激活、失活、失活)的Alpha孔。此外，我想测试一下，其他钾通道(hKv1.2，HERG)是否也能通过Sigma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，并使特定通道调节器的合理设计能够阻断通过Sigma孔的电流。这一点很重要，因为在hKv1.3同源位置388附近的其他钾通道(KCNQ1，HERG，Kir2.1)突变与不同的通道病有关。

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.