Figure 6
Dynamic-clamp injection of I234T conductance can lead to massive depolarization of RMP in native DRG neurons. Simulated wild-type (WTs, A) and mutant (I234Ts, B) hNav1.7 currents. (C) Distributions of RMPs in the following three conditions: no model implemented (native Nav1.7 current), replacing 50% endogenous WT Nav1.7 conductance with an equal amount of WTs current (−50% WTs/ + 50% WTs), and replacing 50% endogenous WT Nav1.7 conductance with an equal amount of I234Ts (−50% WTs/ + 50% I234Ts). (D) The RMP of a cell endowed with I234Ts conductance was depolarized to −24.6 mV (arrow in C). RMP was recorded continuously for 30 s after injecting either 50% WTs or 50% I234Ts Nav1.7 conductance. (E) (upper) In the cell as in (D), an action potential was evoked in response to 200 ms current injection of 500 pA when endowed with WTs conductance. (lower) This cell when endowed with I234Ts conductance, rested at −24.6 mV and failed to produce an action potential; when held at −60 mV in the presence of I234Ts conductance, it regained excitability. (F) In another cell that rested at −51.8 mV, an action potential was generated when current stimulus was increased from 80 pA to 90 pA (upper). When I234Ts was introduced, RMP was depolarized to −46.6 mV and the cell fired spontaneously (lower).
