Inflammatory soup potentiates NaN/Nav1.9 and lowers the threshold of excitability. (A) Current-clamp responses of a Nav1.9+/+ DRG neuron (29 pF) to 3 ms above threshold depolarizing pulse (+800 pA) or 3 ms low intensity depolarizing pulse (+400 pA). (B) Action potential triggered by the above threshold depolarizing pulse in A is shown on an expanded time scale. (C–E) Consecutive segments elapsed by 10 s showing that the subthreshold stimulus elicited action potentials, long-lasting plateau depolarization, and bursts after the addition of the inflammatory soup. The horizontal bar indicates the time and duration of application of the inflammatory soup. (F) Superimposed current-clamp responses to the subthreshold depolarizing currents shown in A (black), C (blue), D (green), and E (red). Note the increase in height and width of the plateau depolarization induced by the inflammatory soup. (G) Quasi steady-state I-V relationships determined by slow voltage ramps (30 mV s−1) before (black), during (red), and after (green, 20 min washout) the application of the inflammatory soup. (bottom) The inflammatory soup–induced TTX-R Na+ current obtained by subtraction displays a threshold of activation of ∼−65 mV. (H) Current-clamp responses of a Nav1.9−/− DRG neuron (21 pF) to 3 ms above threshold depolarizing pulse (+40 pA) before, during, and after the application of the inflammatory soup. Recordings made using the intracellular solution 4 (Table I; 30 mM CsCl, 0 mM CsF, 100 mM KCl).
