Melatonin Modulates Rod Signal In Outer Retinas Of Carp And Rat

Melatonin is involved in regulation of a variety of physiological functions through activating specific G-protein coupled receptors. However, neuromodulatory role of melatonin, released from photoreceptors in the retina, is poorly understood.In the first part, we show that melatonin enhances the sensitivity of the rod signal pathway by potentiating signal transfer from rod photoreceptors to ON type bipolar cells (Rod-ON-BCs) in carp retina. Whole-cell patch-clamp recordings showed that melatonin induced a sustained inward current from Rod-ON-BCs, through activating the melatonin MT₂ receptor, which was identified as one mediated by a cGMP-dependent cation channel. Consistent with it, melatonin was found, using immunocytochemistry, to increase intracellular cGMP levels, which was due to an inhibition of phosphodiesterase. Physiologically, melatonin potentiated responses of Rod-ON-BC to simulated light flashes (brief puffs of CPPG, an mGluR6 antagonist, in the presence of L-AP4, an mGluR6 agonist), which was mediated by cGMP-dependent kinase. Similarly, melatonin increased the amplitude of the scotopic electroretinographic b-wave, a reflection of the Rod-ON-BC activity. These results suggest that melatonin, being at a higher level at night, may improve the signal/noise ratio for rod signal in the outer retina by enhancing signals transfer from rods to BC in fish retina.We further carried on similar experiments with Rod-ON-BCs in rat retinal slices. We found that melatonin suppressed voltage-gated outward potassium currents. Consistent with it, melatonin of 100 nM depolarized the cells by 2-3 mV, which was blocked by TEA (10 mM), suggesting that the TEA-sensitive outward potassium channels were responsive for the melatonin-induced depolarization. Using cell-attached mode, melatonin of 100 nM increased the firing frequency of ON type ganglion cells (ON-GCs). The effects of melatonin were not seen in synaptically isolated ON-GCs, suggesting that melatonin-induced increase in spontaneous firing rates of ON-GCs could be a consequence of depolarization of Rod-ON-BCs.In sum, the present data suggests that melatonin may potentiate signals from rods to bipolar cells in both carp and rat retinas, but the underlying mechanisms may be different.