Figure 3.

Kinetics, voltage dependence, and pharmacology of resurgent and persistent Na⁺ currents in SGNs. A, Family of TTX-sensitive difference currents evoked by 50-ms step depolarization to +14 mV, followed by 200-ms step repolarization to potentials between −16 and −86 mV. Steps to particular potentials are denoted by the colored traces in the voltage protocol. I_NaT was activated during the steps to +14 mV (cropped for clarity). I_NaR activated rapidly on repolarization and then decayed, revealing the noninactivating I_NaP at the end of the test steps. B, Current−voltage (I-V) relationships for maximum TTX-sensitive I_NaR (filled circles) and steady-state I_NaP (open circles; measured between 160 and 190 ms after the onset of the repolarization steps). I_NaR and I_NaP are shown as a percentage of maximum I_NaT recorded in the same cell (n = 30; P12-P14). C, Normalized steady-state conductance-voltage plot for the channels underlying I_NaP (open circles), fitted with a Boltzmann function (n = 23; P12-P14). For comparison, the peak conductance-voltage plot for I_NaT is also shown (discontinuous line, from Fig. 2B). D, The kinetics of activation and decay of I_NaR varied with repolarization potential. During the protocol used in A, repolarization to −76 mV elicited a current with shorter rise time and decay (exponential fit overlaid in red) compared to that elicited by repolarization to −56 mV. E, Mean onset (time to peak) and offset (decay time constant) kinetics of I_NaR in 19 SGNs (P12-P14). F, G, 4,9-ah-TTX, a toxin specific for Nav1.6 subunits blocks I_NaT, I_NaR and I_NaP. F, A depolarizing voltage step to −36 mV activated I_NaT (black trace), which was blocked >70% by bath applied 100 nM 4,9-ah-TTX (red). G, A repolarization from +14 to −46 mV activated I_NaR and I_NaP (black trace), which were both blocked ∼70% by bath applied 100 nM 4,9-ah-TTX (red).