“Four-legged runner” model of the coupling of S4 activation and C-type inactivation. A Kv1.2-2.1 chimera (2R9R) is viewed from the extracellular side. Consistent with the literature, a conformational wave begins with contact between F344 in TMS5 and R293 in TMS4, when the latter is driven outward by voltage. The wave spreads through the illustrated residues to the region of the pore mouth, causing, in susceptible mutants, dilation of the pore mouth and C-type inactivation. The Kv1.2-2.1 chimera does not undergo C-type inactivation because V377 locks Y373 in position; the pore mouth here is not dilated. All of the residues presented as spheres have been shown to affect C-type inactivation. The carbon atoms of these residues are shown using different colors for clarity. TMS1–TMS4 identify the respective transmembrane segments. Prepared using MacPyMol (version 0.99).
