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. 2017 Aug 19;140(10):2570–2585. doi: 10.1093/brain/awx201

Figure 1.

Figure 1

GluCl activation silences electrical activity of DRG neurons in vitro. Whole-cell patch clamp recordings of DRG neurons electroporated with GluClα/β-YFP. (A) GluCl+ DRG neuron. Scale bar = 30 µm. (B) Voltage ramp used to determine membrane conductance. Ivermectin (IVM, 20 nM) treatment induces a membrane conductance in GluCl+ DRG, as seen by the increased slope of the current trace. (C) Induced conductance in response to ivermectin. (Inset) Example recording of ivermectin-conductance over time. One-way ANOVA with post hoc Bonferroni test comparing groups to control (GFP), GFP 5 nM ivermectin n = 10, GFP 20 nM ivermectin n = 10, β-only 5 nM ivermectin n = 11, β-only 20 nM ivermectin n = 15, αβ 5 nM ivermectin n = 24 and αβ 20 nM ivermectin n = 24. (D) Change in input resistance following ivermectin. One-way ANOVA with post hoc Bonferroni test comparing groups to control (GFP), GFP 5 nM ivermectin n = 10, GFP 20 nM ivermectin n = 10, β-only 5 nM ivermectin n = 11, β-only 20 nM ivermectin n = 15, αβ 5 nM ivermectin n = 24 and αβ 20 nM ivermectin n = 24. (E) Firing of neurons in response to supra-threshold current injection pre- and post-ivermectin treatment. (F) Ability of GluCl+ neurons to fire an action potential in response to a short (50 ms) depolarizing current. Neuronal excitability was defined by the fold-increase in rheobase comparing pre- and post-ivermectin values: <3 (excitable), 3–10 (partial silencing) or >10-fold (full silencing). P < 0.001, chi-squared test (χ2 = 55.74 with 4 degrees of freedom). β-only 5 nM ivermectin n = 11, β-only 20 nM ivermectin n = 15, αβ 5 nM ivermectin n = 24 and αβ 20 nM ivermectin n = 24. (G) Excitability of GluCl+ DRG assessed while using an intracellular solution containing 80 mM Cl−. (Left) Example firing of a GluCl+ neuron in response to supra-threshold current stimuli pre- and post-ivermectin (20 nM). (Right) Following ivermectin, 5/5 neurons were unable to fire an action potential in response to a current 10-fold their pre-drug rheobase value (full silencing). All grouped data are mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001; P < 0.0001.