Figure 1.

Panel A shows the schematic topology of a single Kv7.2 subunit, with each of the six transmembrane regions indicated. The green cylinders correspond to the S₅ and S₆ transmembrane regions. The amino acids involved in retigabine binding are indicated. Panel B shows a top view of the overall structure of the channel formed by four identical K_v7.2 subunits, with one retigabine molecule bound. Panel C shows an enlarged view of the retigabine binding site with the retigabine molecule docked into the channel cavity as obtained with ArgusLab 4.0.1 (Planaria Software LLC, Seattle, WA; available at http://www.arguslab.com). The residues involved in retigabine binding are indicated. The dashed yellow lines indicate the polar contacts between retigabine and the residues A235 and W236. Three-dimensional models of K_v7.2 subunits were generated by homology modelling using known structures of potassium channel subunits available in the Protein Data Bank), using SWISSMODEL, a program that performs automated sequence-structure comparisons, as previously described.92 The model generated was analyzed using both the DeepView module of Swiss-PDBViewer (version 3.7, available at http://www.expasy.ch/spdbv/) and PyMOL (available at http://pymol.sourceforge.net/). In the present study, the homology model was built using the template structure (2R9RH) for a chimeric channel in which the voltage-sensor paddle (corresponding to the S_3b–S₄ region) of K_v2.1 was transferred into the K_v1.2 subunit.93