FIGURE 4.

The IFM-motif mediated fast inactivation and the open activation gate. (A) Allosteric inhibition of mammalian Na_V channels by the IFM-motif (PDB code: 6J8I). The pore domain viewed from cytosol is shown in surface. The IFM-motif shown in yellow spheres. (B) Releasing of the IFM-motif leads to channel opening. Activation gate comparison between rat Na_V1.5 (PDB code: 6UZ3) and Na_V1.5/QQQ (PDB code: 7FBS). Red arrows indicate the S6 helix shift. (C) Non-conductive ion path of the inactivated state Na_V channel (PDB code: 6UZ3). (D) Na⁺ conductive ion path of the open-state Na_V channel (PDB code: 7FBS). (E) The open activation gate of Na_V channel provides potential accessing path for the open-state blockers. Propafenone is shown in spheres.