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H. Choi, C. Ribelayga, S. C. Mangel; Roles of cAMP and Protein Kinase A in Circadian Clock Control of Rod-Cone Coupling. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3295.
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A circadian (24-hr) clock in the retina controls rod-cone gap junctional coupling, so that coupling is strong and extensive at night, but weak and restricted during the day (Ribelayga et al., 2008). Because of the clock-induced changes in rod-cone coupling strength, cones and cone-connected horizontal cells receive rod input at night, but not in the day (Wang and Mangel, 1996; Ribelayga et al., 2008). Indirect evidence based on recording the light responses of cone horizontal cells suggests that the clock controls rod-cone coupling through modulation of intracellular cAMP and protein kinase A (PKA) activity in the photoreceptor cells (Ribelayga et al., 2002). Here we directly tested whether manipulating intracellular cAMP and PKA within photoreceptor cells resulted in changes in rod-cone coupling and rod input to cones.
Whole-cell patch-clamp recordings from the inner segments of cones in intact goldfish neural retinas were obtained under continuous dark-adapted conditions during a circadian cycle. Cone responses to dim full-field light stimuli were measured to determine whether they received rod input. The extent of gap junctional coupling between rabbit photoreceptors was assessed by using a cut-loading technique (Ribelayga et al., 2008).
Bath application of forskolin (10 µM), which activates adenylate cyclase, during the subjective day decreased the light response threshold of fish cones by ~2 log units so that the cells responded to low scotopic light stimuli, and increased the extent of rod-cone tracer coupling in the rabbit. In addition, dialysis of fish cones with cAMP (1 mM) during the subjective day decreased their light response threshold by ~2 log units, whereas dialysis of cones with Rp-8-OH-cAMPS (100 µM), a membrane impermeable, selective inhibitor of PKA activity, during the subjective night increased their light response threshold by ~2 log units.
The results indicate that the retinal clock, by elevating cAMP and PKA activity in photoreceptor cells at night, increases rod-cone coupling and rod input to cones, so that cones can respond to low scotopic light stimuli at night.
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