主催: 公益社団法人日本薬理学会
会議名: 第97回日本薬理学会年会
回次: 97
開催地: 神戸
開催日: 2023/12/14 - 2023/12/16
Melatonin is synthesized in and secreted from the pineal glands, which regulates the circadian rhythms. However, the effects of melatonin on pineal ion channels remains unclear. In the present study, the effects of melatonin on voltage-gated K+ (KV) channels in rat pinealocytes were examined by whole-cell patch clamp configuration. The application of melatonin reduced pineal KV currents in a concentration-dependent manner. Expression analysis revealed that KV4.2 channels were highly expressed in rat pineal glands. In HEK293 cells expressed with KV4.2 channels, melatonin decreased outward KV4.2 currents. This inhibition was observed even in the presence of luzindole, an antagonist of melatonin receptors. Melatonin also blocked the activity of KV4.3, KV1.5 and KV1.1 channels in reconstituted HEK293 cells. In pinealocytes treated with KV4.2 siRNA, melatonin-sensitive KV currents were attenuated. Furthermore, the application of melatonin caused membrane depolarization in rat pinealocytes. These results strongly suggest that melatonin directly inhibits KV4.2 channels and results in membrane depolarization in rat pinealocytes.