Under dark-adapted conditions, the release of potassium from proximal retinal neurons is known to depolarize Müller cells and contribute to the STR origin.
25 26 Given the similarities of the large RCS-NPR in the photopic ERG to the enhanced STR that dominates the scotopic ERG of the dystrophic RCS rat, we explored a possible association between K
+ channels and the unusual growth of the RCS-NPR with age. Kir4.1 channels are one of the principal potassium channels on Müller cells,
57 58 and we compared the distribution and density of Kir4.1 channels in RCS and P23H rhodopsin rat retinas using semiquantitative immunohistochemistry. By 14 weeks of age, the RCS dystrophic rats showed an increase in Kir4.1 staining throughout the IPL
(Fig. 9A)compared with earlier ages. Müller cell processes in the proximal retina became more prominent with age and were more heavily labeled with anti-Kir4.1 antibody from the endfeet toward the distal retina, suggesting an increase in the numbers of Kir4.1 channels in this region. Kir4.1 immunolabeling was nearly identical in 6- and 10-week-old RCS dystrophic animals, showing an MPI of 31 ± 3 (mean ± SE,
n = 8), and it increased to 43 ± 4 MPI (
n = 9;
P < 0.05) at 14 weeks
(Fig. 9C) . Kir4.1 labeling colocalized with glutamine synthetase (GS), a marker for Müller cells (
Fig. 9A , inset). Although we cannot rule out the expression of Kir4.1 channels on other elements in the IPL, the high degree of colocalization with GS and the typical appearance of Müller cell processes suggest that Kir4.1 labeling increased on Müller cells with degeneration in the RCS rats. Pigmented Long-Evans control rats showed a small but not statistically significant increase in MPI over this time (32 ± 2 [mean ± SE],
n = 7, at 6 and 10 weeks of age vs. 36 ± 4,
n = 11, at 14 weeks;
P = 0.41) and were not significantly different from RCS rats at any time point. Staining of Kir4.1 channels in the proximal retina did not change over this time in P23H and Sprague-Dawley rats
(Figs. 9B 9D) , and only RCS dystrophic rats showed significantly more staining than P23H rats at age 14 weeks (
P < 0.01; 2-way ANOVA; Bonferroni posttest). Immunolabeling in the RPE of the P23H rats increased from 13.6 ± 2.9 (mean ± SE,
n = 3) at 4 weeks of age to 21.8 ± 4.5 at 8 weeks of age to 31.5 ± 2 at 15 weeks of age; values were significant between 4 and 15 weeks (
P < 0.01 Student’s
t-test).