Skip to main content
. 2018 Jun 27;5(3):ENEURO.0138-18.2018. doi: 10.1523/ENEURO.0138-18.2018

Figure 9.

Figure 9.

Schematic representation of differential nodal destabilization with age. A, P13/14 ablation of AnkG and NF186 during nodal maturation results in a rapid nodal deterioration. By just 5 dpi, AnkG (pink line) is reduced to below 50%, which leads to a dramatic increase in AnkR (blue line). By 10 dpi, AnkG is completely absent from the node, and βIV Spectrin (red line) is being replaced by the AnkR/βI Spectrin complex. As NF186 (green line) levels significantly fall, corresponding reductions are seen in NaV channels (orange line) followed by βIV Spectrin and AnkR. Mice die ∼1 mpi. B, P23/24 ablation of AnkG and NF186 during early nodal maintenance results in a significantly enhanced timeline of nodal destabilization compared to single cKOs. As with P13/14 ablation, AnkG is completely absent from the node by 10 dpi, and the AnkR/βI Spectrin complex has moved in. However, the half-life of NF186 is increased to 1 mpi with P23/24 dual ablation, and corresponding reductions in NaV channels, βIV Spectrin and AnkR reach a peak at 2 mpi, at which point these mice die. C, P93/94 ablation of AnkG and NF186 during late nodal maintenance results in delayed nodal deterioration compared to dual ablation at earlier time points. Although AnkG is still completely absent from the node by 10 dpi and AnkR has begun to move in, the half-life of NF186 is increased to 2 mpi with dual ablation at 3 months of age. Reductions in NaV channels, βIV Spectrin, and AnkR continue until 4 mpi, when mice die. D, P23/24 single ablation of NF186 during early nodal maintenance results in a gradual reduction of NF186 that is not completely lost until 6 mpi. As NF186 levels significantly decline, corresponding reductions are seen in NaV channels, AnkG, AnkR, and βIV Spectrin. Mice die at 6 mpi. E, P23/24 single ablation of AnkG during early nodal maintenance results in a rapid loss of AnkG and increase of AnkR over the first 1 mpi. However, nodal destabilization occurs very slowly, with βIV Spectrin, NaV channels, and NF186 falling below 50% at 10 mpi, at which point these mice die.