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X. Qiu, D. M. Berson; Melanopsin Bistability in Ganglion-Cell Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2007;48(13):612.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsically photosensitive retinal ganglion cells (ipRGCs) use melanopsin as their photopigment. Melanopsin is structurally related to invertebrate opsins which bind retinaldehyde to form bistable photopigments. In such pigments, light generates thermally stable metarhodopsin which retains its all-trans retinal chromophore, and functions as a photoisomerase, absorbing light to regenerate cis retinal and photoexcitable rhodopsin. Though melanopsin is apparently able to form a bistable photopigment, there is no direct evidence that it does so in ipRGCs. We sought such evidence here.
Adult rat ipRGCs retrolabeled from the suprachiasmatic nucleus were recorded by whole-cell current-clamp in isolated retinas. A saturating flash (‘S1’; 480 nm [melanopsin max]; 5s) was followed by a second narrow-band flash (S2).
S1 alone induced a large depolarization that decayed slowly (~2 min) after stimulus termination. Thus, ipRGCs exhibit a persistent depolarizing afterpotential (PDA) like those observed in invertebrate photoreceptors. Invertebrate PDAs are attributed to continued activation of the signaling cascade in the dark by stable metarhodopsin; illumination of appropriate wavelength during the PDA resets Vm toward the resting potential by photoreversing metarhodopsin to rhodopsin, quenching the persistent phototransduction. We observed a similar phenomenon in ipRGCs: S2 could wipe out up to 80% of the PDA. The amount of resetting was graded with intensity. It was greatest shortly after S1 (optimal interval ~7 sec). At longer intervals, the resetting effect of S2 dwindled and was eventually supplanted by depolarizing photoexcitation. Photoreversal was spectrally dependent, with an optimum near 560 nm. These phenomena were evident under voltage clamp and when synaptic transmission was blocked, indicating that they are not dependent on Vm or retinal circuitry.
Melanopsin forms a bistable photopigment in ipRGCs. As in rhabdomeric photoreceptors, the PDA is apparently due to the persistence of a photoexcited ‘metamelanopsin’ species that is vulnerable to depletion by photoreversal, but also decays gradually in darkness. The absorption spectrum for metamelanopsin is shifted to longer wavelengths with respect to that for melanopsin.
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