Combined Changes in Chloride Regulation and Neuronal Excitability Enable Primary Afferent Depolarization to Elicit Spiking without Compromising its Inhibitory Effects
Fig 5
PAD-mediated inhibition in DRG neurons.
(A) Sample responses from a typical neuron made hyperexcitable by 4-AP and virtual sodium conductance (ḡNa = 0.3 nS/pF). The repetitive spiking elicited by the Istim step was reduced by application of a small gGABA step (middle row) and was altogether stopped by larger gGABA steps (top row). For equivalent ḡGABA, stronger inhibition was evident with EGABA = -35 mV than with EGABA = -20 mV (compare left and right columns). (B) Sequence of Istim and gGABA steps was changed to verify that the latter could elicit transient spiking yet still inhibit the repetitive spiking driven by Istim. Note that repetitive spiking starts after the gGABA step ends and lasts until the Istim step ends. (C) PAD-mediated inhibition of transient spiking was assessed using the same protocol as in B but we varied the amplitude of the Istim step to determine rheobase (i.e. the minimum Istim required to evoke spiking). Only responses to rheobasic stimulation are shown. Note that rheobase increases with increases in ḡGABA, whereas spike height decreases. (D) Change in rheobase (mean ± SEM) is plotted against ḡGABA for EGABA = -35 mV (blue, n = 3 cells) and -20 mV (red, n = 4 cells). Rheobase was significantly increased by ḡGABA (p = 0.013, one-way repeated measures ANOVA; p = 0.013 (*), p = 0.002 (**), Holm-Sidak post-hoc tests vs no gGABA) but EGABA did not have a significant effect (p = 0.52).