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

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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.