Figure 2.

Na_V1.8 contributes to action potential overshoot, half-width, and repetitive firing. (A) Representative traces from the same iPSC-SN illustrating the action potential waveform in the setting of varying levels of Na_V1.8 current density. (B) Increasing Na_V1.8 current density increases the overshoot of iPSC-SNs, although the effect is more robust at lower initial overshoot amplitudes. For neurons with an initial overshoot amplitude between 40 and 45 mV (far left), the change in overshoot is best fit with a linear model with slope 0.1706 and an r² of 0.5093. For neurons with an initial overshoot between 45 and 50 mV (center-left), 50–55 mV (center-right), and 55–60 mV (far right), the change in overshoot amplitudes are best fit with exponential association equations. (C) Increasing Na_V1.8 current density directly increases the action potential half-width of iPSC-SNs linearly (% change in half-width = 0.4254*current density) with an r² of 0.65. An equivalent transformation of the data into base-10 logarithmic form illustrates a similarly robust relationship (% change in half-width = 0.4816*e^{2.253(log[current density])}) with an r² of 0.6502. (D) Increasing Na_V1.8 current density enhances iPSC-SN repetitive firing following (Δ action potential count = 524.9*(1 − e^{−0.002266(current density)}) with an r² of 0.4164. (E) Representative traces depicting the response of the same iPSC-SN to a 1 s duration 500 pA suprathreshold stimulus with no Na_V1.8 currents injected via dynamic clamp (left), approximately 50 pA/pF Na_V1.8 current density (middle), and 100 pA/pF current density (right).