Figure 4.

Neuronal Na⁺ Channels and RyR2 Colocalize to the Same Discrete Subcellular Regions

(A) Representative confocal micrographs of isolated CPVT ventricular myocytes labeled for RyR2 (red) with various Na_v isoforms (Na_v1.x, green) often resulted in an overlap between the immunofluorescent (IF) signals (yellow) when overlaid. (Right) Close-up views of regions highlighted by dashed white boxes. (B) Representative confocal micrographs of ventricular myocytes isolated from CPVT mice showing fluorescent proximity ligation assay (PLA) signal for RyR2 with different nNa_v isoforms (Na_V1.x). Below each image are the results of digital segmentation, with the cell mask in gray and PLA signal in red. (C) Plot of average number of PLA punctae/μm² (p < 0.001 Kruskal-Wallis test; *p = 0.002, ∗p = 0.019, ∗p < 0.001 Wilcoxon rank sum test for Na_v1.6 vs. Na_v1.1, 1.3, and 1.5, respectively; n = 1,231, 1,223, 1,291, and 2,848 punctae from 7, 6, 12, and 7 cells for Na_v1.1, 1.3, 1.5, and 1.6, respectively). Abbreviations as in Figure 1.