Melatonin receptors activate heteromeric G-protein coupled Kir3 channels.

The effects of melatonin on circadian pacemaker activity in the central nervous system may be the result of melatonin receptor activation of G-protein coupled potassium channels which inhibit the action potential firing of neurons. Xenopus laevis and human1a melatonin receptors stimulated heteromeric G-protein activated inwardly rectifying potassium channels (Kir3.1/Kir3.2) when expressed in vitro in oocytes. Pertussis toxin reduced iodo-melatonin (87.1% reduction) and melatonin (90.3% reduction) stimulated currents in a time-dependent manner for cells expressing X. laevis receptors. A similar pertussis toxin inhibition was observed for human melatonin receptors (melatonin, 78.9% reduction). This suggests a potential role for heteromeric Kir3 channels in the receptor-mediated actions of melatonin in vivo.