MELATONIN RECEPTORS ACTIVATE HETEROMERIC G-PROTEIN COUPLED KIR3 CHANNELS

THE effects of melatonin on circadian pacemaker activity in the centra l nervous system may be the result of melatonin receptor activation of G-protein coupled potassium channels which inhibit the action potenti al firing of neurons. Xenopus laevis and human(1a) melatonin receptors stimulated heteromeric G-protein activated inwardly rectifying potass ium channels (Kir3.1/Kir3.2) when expressed in vitro in oocytes. Pertu ssis 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.