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Z. Chen, Z. Yin, L. Chen; The Properties of Voltage-Activated Sodium and Potassium Channels of Retinal Ganglion Cells in RCS Rats During Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4420. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the properties of voltage-activated sodium and potassium currents of RCS rat retinal ganglion cells during retinal degeneration, and to study the pathophysiological mechanisms of inner retinal neuronal degeneration following the loss of photoreceptors.
Retinal dystrophic RCS rats (RCS-P+) were examined on postnatal days 21 (P21), P60; P90; non-dystrophic RCS rats (RCS-rdy+-P+) aged P21 and P90 were used for comparison. Retinal slices were prepared and data obtained using whole-cell patch clamp recording. The voltage-activated sodium and potassium currents were recorded under voltage clamp mode during the application of channel blockers. Amplitude, current density, I-V curves and their relationship to action potentials (APs) were analyzed. Immunohistochemistry (anti-VGSC) and Western blots were used to assess the expression of RGCs sodium channels.
Transient firing and sustained firing of RGCs in response to depolarizing currents were recorded at P21. At this age there were no significant differences in the current amplitude and density of dystrophic (N=22) and normal RCS rats (N=16). However, at later stages of retinal degeneration, we could only evoke APs from 67% of RGCs (12/18); retinal dystrophic RCS rats at P60, and the amplitude and density of sodium currents decreased dramatically. Significant changes in potassium currents were not observed. Sodium currents were not present and only reduced potassium currents were seen in RGCs unless APs were recorded. In normal and early RCS-P+ rats the RGC layer was clearly stained by VGSC; but at later ages only weak staining was seen in RCS-P+ rats. Quantitatively, the expression of the sodium channel was dramatically reduced during these stages of degeneration.
Our results suggest that the density of voltage-dependent sodium channels and their associated proteins in RGCs are depleted in the later stages of retinal degeneration. Potassium channels involvement appeared to be more moderate, but was also impaired. In addition, our data indicates that the sodium channels are dysfunctional following the loss of photoreceptors in the dystrophic RCS rats. The loss of sodium channel function may be a molecular mechanism of the inner retina that triggers neuronal degeneration.
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