Skip to main content
. Author manuscript; available in PMC: 2020 Feb 15.
Published in final edited form as: Circ Res. 2019 Feb 15;124(4):539–552. doi: 10.1161/CIRCRESAHA.118.314050

Figure 7: Proposed updated VSD-modulated receptor model for Class Ib antiarrhythmics.

Figure 7:

The model comprises five states, CR, CA, OA, IA, and IR. R and A represent the DIII-VSD at resting and activated positions, respectively. C, O, and I represent closed, open and inactivated states of the pore. Mexiletine has different binding affinity to each state. Thick arrows represent high binding affinity, and the thin black arrows represent low binding affinity. After mexiletine blocks the pore, channels enter five drug modulated states, CR*, CA*, OA*, IA*, and IR*. The transition rates between modulated states change compared to those between the unmodulated states. This model provides a molecular basis for how mexiletine preferentially blocks the channel when the DIII-VSD is activated (CA, OA, IA).