By challenging specific receptors, melatonin synthesized and released by photoreceptors regulates various physiological functions in the vertebrate retina. Here, we studied modulatory effects of melatonin on K+ currents of rod-dominant ON type bipolar cells (Rod-ON-BCs) in rat retinal slices by patch-clamp techniques. Double immunofluorescence experiments conducted in isolated cell and retinal section preparations showed that the melatonin MT2 receptor was expressed in somata, dendrites and axon terminals of rat Rod-ON-BCs. Electrophysiologically, application of melatonin selectively inhibited the tetraethylammonium (TEA)-sensitive K+ current component, but did not show any effect on the 4-aminopyridine (4-AP)-sensitive component. Consistent with the immunocytochemical result, the melatonin effect was blocked by co-application of 4-pheny1-2-propionamidotetralin (4-P-PDOT), a specific MT2 receptor antagonist. Neither protein kinase A (PKA) nor protein kinase G (PKG) seemed to be involved because both the PKA inhibitor Rp-cAMP and the PKG inhibitor KT5823 did not block the melatonin-induced suppression of the K+ currents. In contrast, application of the phospholipase C (PLC) inhibitor U73122 or the protein kinase C (PKC) inhibitor bisindolylmaleimide IV (Bis IV) eliminated the melatonin effect, and when the Ca2+ chelator BAPTA-containing pipette was used, melatonin failed to inhibit the K+ currents. These results suggest that suppression of the TEA-sensitive K+ current component via activation of MT2 receptors expressed on rat Rod-ON-BCs may be mediated by a Ca2+-dependent PLC/inositol 1,4,5-trisphosphate (IP3)/PKC signaling pathway. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
[1]Fudan Univ, Inst Brain Sci, Inst Neurobiol, Shanghai 200032, Peoples R China.
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