Melatonin promotes sleep by activating the BK channel in C. elegans.

Longgang Niu, Yan Li, Pengyu Zong, Ping Liu, Yuan Shui, Bojun Chen, Zhao-Wen Wang

Proceedings of the National Academy of Sciences of the United States of America 2020 Oct 06

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Melatonin (Mel) promotes sleep through G protein-coupled receptors. However, the downstream molecular target(s) is unknown. We identified the Caenorhabditis elegans BK channel SLO-1 as a molecular target of the Mel receptor PCDR-1-. Knockout of pcdr-1, slo-1, or homt-1 (a gene required for Mel synthesis) causes substantially increased neurotransmitter release and shortened sleep duration, and these effects are nonadditive in double knockouts. Exogenous Mel inhibits neurotransmitter release and promotes sleep in wild-type (WT) but not pcdr-1 and slo-1 mutants. In a heterologous expression system, Mel activates the human BK channel (hSlo1) in a membrane-delimited manner in the presence of the Mel receptor MT1 but not MT2 A peptide acting to release free Gβγ also activates hSlo1 in a MT1-dependent and membrane-delimited manner, whereas a Gβλ inhibitor abolishes the stimulating effect of Mel. Our results suggest that Mel promotes sleep by activating the BK channel through a specific Mel receptor and Gβλ.

Citation

Longgang Niu, Yan Li, Pengyu Zong, Ping Liu, Yuan Shui, Bojun Chen, Zhao-Wen Wang. Melatonin promotes sleep by activating the BK channel in C. elegans. Proceedings of the National Academy of Sciences of the United States of America. 2020 Oct 06;117(40):25128-25137