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

在通道突变体（hKv1.3_V388C）中的哺乳动物特异性hKv1.3钾通道的背景下，在我的实验室中可以记录到意外的电流。该电流既不流过电压敏感域中的中央α孔，也不流过Ω孔。我想知道，我们命名为sigma-pore的电流通路是否确实在α-pore后面运行，或者这个电流通路是否仍然通过具有新的，修改的α-pore特征（选择性，激活，失活，失活）的α-pore。此外，我想测试，是否其他钾通道（hKv1.2，hERG）也能够通过σ孔产生电流。这些计划中的实验的结果应该增加我们对钾通道的功能通道结构的了解，并使特定通道调节剂的合理设计成为可能，能够阻断通过σ孔的电流。这一点很重要，因为其他钾通道（KCNQ 1，hERG，Kir2.1）中与hKv1.3中同源位置388非常接近的突变与不同的通道病相关。

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.