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Allison M. Sargoy, Steven A. Barnes, Nicholas Brecha; Depolarization-induced Calcium Signals In Ganglion Cell Axon Fibers Mediated By Voltage-gated Ca Channels. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4573.
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Increased Ca2+ levels in retinal ganglion cell (RGC) somas lead to cell degeneration, decreased visual acuity, and loss of vision. RGC axons project from the retina to the brain and are considered the primary site of injury in several forms of RGC trauma. Previous studies suggest that blocking Ca channels can reduce the loss of RGCs in response to trauma of the optic nerve. The goal of this study is to investigate the contribution of voltage-gated Ca channels to Ca2+ signals in RGC axon fibers.
Whole-mount retinas from Sprague Dawley rats were imaged on a Zeiss Pascal laser scanning confocal microscope. RGCs and RGC axons were labeled retrogradely with Fluo-4 pentapotassium salt injected at the optic nerve stump. Retinas were depolarized by superfusion with 60 mM K+ for 50 s, and were treated with Ca channel blockers including nifedipine (Nif), an L-type Ca channel blocker, ω-conotoxin-GVIA, an N-type Ca channel blocker, and cadmium and cobalt, which block all voltage-gated Ca channels.
Fluo-4 robustly labeled bundles of RGC axons and high K+-evoked Ca2+ signals were seen as transient increases in fluorescence. 10 µM Nif reduced the high K+-evoked Ca2+ signals in the RGC axons by 22% (p<0.05), an effect stronger than that of conotoxin which at 1.5 µM reduced the signal by 14% (p<0.05). 200 µM CdCl2 reduced the signal by 30% (p<0.05) while 1 mM CoCl2 reduced high K+-evoked Ca2+ signals in the RGC axons by 88% (p<0.05).
These results show that within RGC axons, voltage-gated Ca channels can be activated by depolarization and that these Ca channels appear to account for most of the Ca2+ influx. Different degrees of block by Nif, conotoxin, and cadmium suggest that selective pharmacological agents could promote RGC survival by inhibiting the influx of Ca2+ into the axons following damage to the optic nerve.
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