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Hee Joo Choi, Yu Cao, Adewunmi Adelaja, Leslie Adams, Christophe Ribelayga, Stuart Mangel; GABA-A Receptors Are Expressed And Active On Cones To A Greater Extent At Night, Than In The Day. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4109.
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The expression and function of GABA receptors on cone photoreceptor cells remain unclear and controversial. Because 1) GABAA receptor (GABAAR) expression and activity are increased when intracellular cAMP/PKA increases (Jacob et al., 2008) and 2) the circadian (24-h) clock in the retina increases intracellular cAMP/PKA in photoreceptor cells at night, compared to the day (Iuvone et al., 2005), we examined whether GABAAR expression and activity on cones are increased at night, compared to the day.
Pigmented rabbits and goldfish were bright light (photopic)-adapted for 1 h in the day or dark (low scotopic)-adapted for 1 h in the day or night. Retinal sections were processed in an identical manner for immunostaining with specific antibodies against the β2/3 subunit-containing GABAAR (rabbits: bd-17; fish: 62-3G1) and the Cl-cotransporters KCC2 (B22), and NKCC (T4). Double labeling with cell type-specific antibodies determined co-localization of GABAARs, KCC2 and NKCC on cone terminals (PNA) and bipolar cell (BC) (ON-BCs: Goalpha; OFF-BCs: GluR5) and horizontal cell (HC) (calbindin) dendrites. The effects of picrotoxin, a GABAA/C antagonist, on cones in intact goldfish neural retinas were studied in the day and night using whole-cell patch-clamp recording.
In both rabbits and fish, intense GABAAR, KCC2 and NKCC antibody labeling were observed in the OPL in the day following prolonged light adaptation, but these immunosignals were minimal in dark-adapted retinas in the day. Following light adaptation in the day ON-cone BC and HC dendrites expressed GABAARs and NKCC and OFF-cone BC dendrites expressed GABAARs and KCC2. Interestingly, intense GABAAR and KCC2, but not NKCC, antibody labeling were observed in the OPL at night following prolonged darkness and were primarily restricted to cones. Picrotoxin increased the input resistance of goldfish cones at night, but had minimal effect on cones during the day following prolonged light or dark adaptation.
The results suggest that GABAARs and KCC2 are expressed on cones and are functional to a greater extent at night under dark-adapted conditions, compared to the day following either light or dark adaptation. The findings are also consistent with the idea that the retinal clock, by elevating cAMP and PKA activity in cones at night, increases GABAAR and KCC2 expression, so that GABAAR-mediated feedback from HCs to cones is more effective at night, compared to the day.
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