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Y. Cao, C. Ribelayga, S. C. Mangel; Light/Dark Adaptation Regulates Chloride Cotransporter Expression and the Receptive Field Surround. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1520. doi: https://doi.org/.
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Retinal ganglion cells (GCs) display a center-surround receptive field organization under light-adapted conditions, but GCs lose their surround responses following 30-40 min of dark adaptation (Barlow et al., 1957; Muller & Dacheux, 1997). Under light-adapted conditions, horizontal cells (HCs) contribute to GC surround responses (Mangel, 1991) possibly by releasing GABA onto bipolar cells (BCs), which express chloride (Cl)-permeable GABA-A receptor channels. If GABA-A receptors mediate the surround responses of BCs (and GCs), then GABA could depolarize ON-BCs and hyperpolarize OFF-BCs via the Cl cotransporters Na-K-Cl (NKCC), which accumulates intracellular Cl, and K-Cl (KCC), which extrudes Cl, respectively. Although NKCC and KCC2 have been localized to the dendrites of ON- and OFF-BCs, respectively (Vardi et al., 2000), their role in generating surround responses remains unclear. Moreover, little is known regarding how GCs lose their antagonistic surround responses following dark adaptation.
Rabbits and goldfish were light- or dark-adapted for 1 hr or rabbit and goldfish retinas were incubated in Ringer for 1 hr under light-adapted conditions with or without test drugs. Retinal sections were then processed in an identical manner for immunostaining with specific NKCC (T4, DSHB) and KCC2 (B22, Upstate) antibodies. Antibody specificity was confirmed with western blotting. In addition, the effects of current injections into rabbit HCs on the extracellular spike activity of nearby GCs were studied using standard electrophysiological techniques.
Intense NKCC and KCC2 antibody labeling was observed in the outer plexiform layer (OPL) of light-adapted rabbit and goldfish retinas under control conditions. However, in the OPL of dark-adapted retinas or in the OPL of light-adapted retinas pre-treated with either the dopamine D1 antagonist SCH23390 or the nitric oxide (NO) synthase inhibitor L-NAME, NKCC and KCC2 immunoreactivity was much less intense. In the rabbit retina under light-adapted conditions, bumetanide, a specific NKCC inhibitor, but not furosemide, a specific KCC inhibitor, blocked the sign-conserving effect of HC current injections on the spike activity of nearby ON-center GCs.
Our results suggest that 1) NKCC and KCC2 expression in the OPL are significantly greater following light adaptation compared to dark adaptation due to light-induced activation of D1 receptors and NO synthesis and 2) HCs drive ON-center GCs (via ON-center BCs) in light-adapted retinas in a sign-conserving and NKCC-dependent manner.
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