Effect of melatonin on membrane conductance in CHO cells expressing the human mel_1a melatonin receptor

Activation of mammalian, melatonin receptors appear to regulate circadian rhythms (mel_1a), visual function (mel_1b) and vascular contractility (mel_1a). Here we examined changes, in membrane conductances mediated by activat-ion of the human mel_1a melatonin receptor stably expressed in CHO cells. Melatonin (1 pM-0.1 μM) did not affect basal production of cAMP or ionic conductances, as determined by whole-cell patch clamp. Membrane con-ductances were decreased by TEA (100 μM), a blocker of large conductance calcium-activated potassium channel (BK_Ca), and were increased by NS 1619, a BK_Ca channel activator. Furthermore, incubation with the perme-able cAMP analogue, chlorophenylthio-cAMP, altered membrane conduc-tances. Activation of the mel_1a receptor by melatonin (1 pM-1μM) decreased the forskolin stimulated cAMP production und protein kinase activity in mel_1a-CHO cells. Under whole-cell patch clamp the increases in membrane conductances mediated by forskolin (100 μM) were decreased by bath application of melatonin. These results suggest that melatonin-receptor activation inhibits cAMP-mediated changes in membrane conductance. The involvement of BK_Ca channels in the mechanism(s) of melatonin receptor-mediated changes in membrane con-ductances in mel_1a-CHO cells is under investigation.