title: Melatonin inhibits tetraethylammonium-sensitive potassium channels of rod ON type bipolar cells via MT2 receptors in rat retina.
abstract: 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-phenyl-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.
authors.affiliation: Institutes of Brain Science, Institute of Neurobiology and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, PR China.
authors.forename: X-F
authors.initials: XF
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Miao
authors.forename: Y
authors.initials: Y
authors.lastname: Ping
authors.forename: H-J
authors.initials: HJ
authors.lastname: Wu
authors.forename: X-L
authors.initials: XL
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044123:Receptor, Melatonin, MT2 / Q000378:metabolism*; D051245:Retinal Bipolar Cells / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019789:Tetraethylammonium / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D044123:Receptor, Melatonin, MT2; D019789:Tetraethylammonium; D008550:Melatonin