Proposed model of Kv1.2 activation based on TMRM fluorescence. (A) Closed state structure of Kv1.2 A291C-TMRM based on the closed state model of Pathak et al. (2007), shown from the top. Only one voltage-sensing domain (yellow) and the pore domain from an adjacent subunit (green) are shown. Residues tested are labeled and highlighted based on their ability (blue) or inability (orange) to yield voltage-dependent fluorescence; the A291C mutation is shown in red. The TMRM molecule is modeled within the external aqueous vestibule between S4 and S1–S3 as a spherical structure of carbon (green), oxygen (red), and nitrogen (blue) atoms. (B) Open state structure of Kv1.2 A291C-TMRM. The view shown, looking down on the channel, is similar to that in A for the closed state channel relative to the pore domain, in particular S5. (C and D) Side views of the closed and open state structures of Kv1.2 A291C-TMRM seen in A and B. Transmembrane helices of one subunit are as labeled in each panel.