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. 2016 Mar;147(3):229–241. doi: 10.1085/jgp.201511517

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© 2016 Corbin-Leftwich et al.

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Figure 6. — Proposed kinetic scheme for the activity of K_V7.2/K_V7.3 and the effect of Retigabine. The scheme contains five global states, which are different with respect to each other depending on the activation status of the VSD and the pore domain (P). In the scheme, VSD represents the four voltage sensors of the channel. At negative potentials, the VSDs are in the deactivated state (VSD_D) and the pore is, therefore, closed (P_C0). Upon depolarization, the VSDs are activated (VSD_A), allowing the pore to sojourn between a conductive and a nonconductive state (P_O1 and P_C1, respectively). Holding the membrane depolarized potentials keeps the VSDs in the VSD_A state while allowing a second transition in the pore. As a result, the pore sojourns between a second pair of conductive and nonconductive states (P_O2 and P_C2, respectively) and the channel becomes Retigabine sensitive. Deactivation from these states is slower than from the pair P_C1–P_O1. Retigabine further decreases the rate of deactivation from the pair P_C2–P_O2 while leaving deactivation unaffected from the other pair.