Melatonin inhibits tetraethylammonium-sensitive potassium channels of rod ON type bipolar cells via MT2 receptors in rat retina
Melatonin inhibits tetraethylammonium-sensitive potassium channels of rod ON type bipolar cells via MT2 receptors in rat retina
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DOI：
10.1016/j.neuroscience.2010.11.028
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发表时间：
2011-01
期刊：
影响因子：
3.3
通讯作者：
X.-F. Yang;Y. Miao;Y. Ping;H.-J. Wu;X.-L. Yang;Z. Wang
中科院分区：
文献类型：
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作者：
X.-F. Yang;Y. Miao;Y. Ping;H.-J. Wu;X.-L. Yang;Z. Wang
通过挑战特定的受体，光感受器合成和释放的褪黑素调节脊椎动物视网膜的各种生理功能。在此，我们用膜片钳技术研究了褪黑素对大鼠视网膜脑片视杆优势型双极细胞(Rod-on-BCs)钾电流的调制作用。在分离的细胞和视网膜切片上进行的双重免疫荧光实验表明，褪黑素MT2受体在大鼠Rod-on-BCS的胞体、树突和轴突终末均有表达。电生理上，褪黑素选择性地抑制四乙基铵(TEA)敏感性钾电流成分，但对4-氨基吡啶(4-AP)敏感性成分无影响。与免疫细胞化学结果一致的是，褪黑素的作用可被MT2受体特异性拮抗剂4-苯基-2-丙酰胺四氢呋喃(4-P-PDOT)联合应用所阻断。蛋白激酶A(PKA)和蛋白激酶G(PKG)似乎都不参与，因为PKA抑制剂RP-cAMP和PKG抑制剂KT5823都不能阻断褪黑素对K+电流的抑制作用。相反，应用磷脂酶C(PLC)抑制剂U73122或蛋白激酶C(PKC)抑制剂双吲哚马来酰亚胺(Bis IV)可消除褪黑素的作用，而当使用含钙离子螯合剂BAPTA的移液管时，褪黑素不能抑制K+电流。这些结果提示，通过激活大鼠Rod-on-BCS上表达的MT2受体来抑制TEA敏感的K+电流成分，可能是通过钙依赖的PLC/IP3/PKC信号通路来实现的。
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 MT2receptor 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 MT2receptor 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 MT2receptors expressed on rat Rod-ON-BCs may be mediated by a Ca2+-dependent PLC/inositol 1,4,5-trisphosphate (IP3)/PKC signaling pathway.