Figure 1.

Schematic representation of the voltage-gated sodium channel (VGSC) with major kdr mutations discussed in the present work. S1–S4 segments: voltage-sensing domains; S5-S6 segments and connecting loop: pore-forming domains. Physiologic mechanism: (i) after depolarization, S4 segments (in grey) open the gate moving outward (activation). (ii) Then, residues in the linker domains III-IV constitute an inactivation particle allowing channel inactivation (inner pore block). (iii) Following repolarization, the S4 segments close the gate (deactivation).