Melatonin is sometimes used to treat sleep disorders owing to its effects on circadian rhythms, but the underlying mechanisms are not known. In this study, knockout of G-protein-coupled inwardly rectifying potassium channel 2 (GIRK2) in mice reduced the phase-advancing effects (in which the onset of behavioural activity started at an earlier time) of melatonin on wheel-running behaviour and reduced spontaneous firing frequency in suprachiasmatic nucleus neurons, suggesting that melatonin activation of GIRKs is sufficient to affect circadian rhythms.
Hablitz, L. M. et al. GIRK channels mediate the nonphotic effects of exogenous melatonin. J. Neurosci. 35, 14957–14965 (2015)
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Lewis, S. Melatonin influence on circadian rhythms. Nat Rev Neurosci 17, 4 (2016). https://doi.org/10.1038/nrn.2015.11