Journal: Experimental eye research

Article Title: Elevated ocular pressure reduces voltage-gated sodium channel NaV1.2 protein expression in retinal ganglion cell axons

doi: 10.1016/j.exer.2019.107873

Figure Lengend Snippet: Assessment of NaV1.2 channel protein level and physiology in retinal ganglion cells. (A) NaV1.2 (red) is expressed along retinal ganglion cell (RGC) axon proximal sections (dashed line segment) as identified by SMI32 (green) and z-axis depth within whole mount retinas. NaV1.2 is also localized within distal axons (arrowheads) marked by SMI32. (B) Intensity profiles of NaV1.2 and SMI32 along the axon proximal segment indicated in A. The heavy dashed horizontal line indicates mean intensity for each signal. (C) NaV1.2 is localized within varicosities of distal axons (arrowheads). (D) Overlap of NaV1.2 and SMI32 signals within distal axon example shown in C. The heavy dashed horizontal line marks the mean intensity for each signal. (E) NaV1.2 outlines Brn3a-positive (blue) somas. (F) NaV1.2 intensity profile of example RGC soma (dashed square) shown in E. Scale bar = 10μm. (G) Example light-evoked trace from a typical αON-sustained RGC prior to blockade of NaV1.2. (H) The NaV1.2-specific blocker, Phrixotoxin-3 (Phx3), reduces light-evoked spiking in a dose-dependent manner in an example ON-sustained RGC (histogram bin width = 300 ms). (I) Light-evoked spike rate was normalized to pre-drug light response for each cell (n=10). Spike rate was significantly (*, p≤0.04) reduced by application of 25nM Phx3, and spiking was completely abolished by 400nM for all cells analyzed. Solid line is the best-fit exponential decay (R2=0.88). Based on the exponential decay function 40nM Phx3 would reduce the light-evoked spike rate by 50% (Ic50, dashed gray line). The heavy solid gray horizontal lines in G and H indicates light duration (3 s). Data represented as mean ± sem. Statistics: One-Way ANOVA, Tukey Post-hoc comparisons.

Article Snippet: NaV1.2 channels were modulated by bath application of 25-400nM Phrixotoxin-3 (Alomone labs ( Bosmans et al., 2006 )).

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