Figure 5.

Increased K⁺ and Ca²⁺ Current Density in DEF versus WT DRGNs

(A)Whole-cell onward K⁺ currents were elicited using depolarizing steps from −110 to 40 mV (ΔV = 10 mV). The tail currents were at −40 mV. Current traces recorded from WT and DEF DRGNs are shown in black and blue, respectively. To obtain a profile of currents that are enhanced in DEF DRGNs, we determined the “difference currents” between DEF and WT neurons at −70 and 40 mV step voltages (traces are plotted with dashed lines in inset).

(B) Summary of steady-state currents was normalized to individual membrane capacitance (C_m), from 6-month-old WT mice (shown with black line and symbol) and DEF (shown with gray traces). Data were generated from 14 DRGNs from each experimental group. The mean current densities (in pA/pF) in WT and DEF DRGNs at 0 mV step voltage were 26.1 ± 2.6 and 39.9 ± 2.8; n = 14, p = 0.0015.

(C and D) Inward Ca²⁺ currents recorded from a 12-pF DRGNs in WT (in black) and DEF (in blue) mice from −90 and −40 mV holding potentials. Currents were generated using voltage steps ranging from −110 to 40 mV. The difference-current traces (−90 mV) - (−40 mV) are plotted in dashed lines as an inset.

(E) Peak Ca⁺ current density (I)-voltage (V) relation from data amassed from 12 DRGNs in each group. The current densities generated from a holding voltage of −40 mV are plotted with WT in black and DEF in blue. The high-voltage activated component of the Ca²⁺ current was enhanced in the DEF DRGNs. The peak current density (in pA/pF) for currents elicited from a holding potential of −40 mV for WT DRGNs was 20.1 ± 1.5 (n = 9) and for DEF DRGNs was 30.9 ± 2.5 (n = 9, p = 0.002). After application of 500 nM rSNX-482 to the DEF DRGNs the peak current density plummeted to 12.6 ± 1.2 (n = 6, p< 0.0001).